The Binding of Isaac is a hybrid Roguelike/Zelda-like Top-Down Shooter made by Edmund McMillen and Florian Himsl, released in September 2011.The story follows Isaac, a young boy who finds himself in possibly the worst situation imaginable. After his fanatical Christian mother begins hearing the voice of God, she removes all of his worldly possessions and strips him naked, confines him to his bedroom, and unthinkingly accepts a commission to kill him in sacrifice to prove her devotion. Isaac discovers her intentions and manages to escape into the basement, where, still naked, he goes on the run as he fights off nightmares both physical and mental (using his own tears, no less), discovers secrets about his mother's past, and ultimately confronts her in an effort to survive.An expansion, Wrath of the Lamb, came out in May 28th of 2012. It adds a new category of collectibles called "trinkets," plus new and upgraded items, enemies, bosses, alternate areas, room types, a new character, a new ending and more. It has a trailer. Be afraid.An Updated Re-release, The Binding of Isaac: Rebirth, is in development, and is planned to be released for both PC and consoles (Edmund has made a blog post on it here, or catch this interview (and then another one) with Northernlion).
The Dead Cat gives you nine extra lives, but your health is reduced to one heart on pickup. You also revive with only one heart. There's nothing stopping you from earning more, of course. Unfortunately, your health is reset to one heart every time you die.
100% Completion: The "Golden God" achievement is obtained for getting all the items in the game. The "Platinum God" achievement is a step further: you need to collect all items from the vanilla game and Wrath of the Lamb. If you started off with the DLC, though, you're likely to end up getting both at the same time.
20% More Awesome: The video announcement for the Halloween update states that the game is now '20% more evil'.
Abnormal Ammo: Not just his tears, through upgrades Isaac can shoot: flies, blood, teeth, urine, chocolate milk, ghost tears, explosive vomit and more.
All Just a Dream: The first time you defeat Mom, the victory narration is revealed to be just a story Isaac is drawing. She's still coming.
Normally, treasure rooms are locked and require a key for entry. The exception is the treasure room on the very first floor, as there are few rooms on that floor, making the event of finding a key rather uncertain. Unfortunately, this is not the case if the player gets Curse of the Labyrinth, which combines the first and second floors into one. Here, both treasure rooms will be locked.
The No Damage Run achievements only require you to beat the bosses. This means you can take the shortest path to the boss rooms to avoid damage. It also takes effect when you beat the boss, so you can go back after getting the achievement without having to worry about taking damage.
Artificial Stupidity: The Meat Boy familiar will eat your enemies for breakfast... if only it didn't occasionally get stuck chasing after and ineffectually biting enemies that are invincible (for example, the Mask part of the Mask-Heart monster).
Ascended Extra: Isaac's pet Guppy is only seen in Isaac's will and some items. If you get three of said items, you turn into Guppy (giving you flight and the same fly-spawning ability as The Mulligan, if said ability was on steroids).
Asteroids Monster: Envy, Blastocyst, Fistula and Teratoma, and to a lesser extent the double flies.
The Dr. Fetus powerup. Good luck trying to kill hosts with it. The Ipecac Syrup, added in the expansion, is even more Awesome But Impractical — it launches the same green spit bombs as the green enemies do. It can blow open doors and poisons enemies, but on the other hand, it travels in an arc that can make it very difficult to work with, especially on faster enemies. It also explodes when traveling over a rock, even when it's visibly meters above it, so it will blow up in your face. Of course, just like Brimstone, mastery of such items can make them Difficult, But Awesome.
Several rare items, particularly in combination with each other, would be awesome... except finding them all in the same playthrough is unlikely due to the randomized nature of the game.
When Isaac is down to his last half-heart, The Scapular item grants a last-gasp reprieve of one soul heart. When combined with the Cursed Skull trinket, the player is functionally invincible at the cost of having to re-attempt the room he died in from the start. Good luck fighting Mom under no-hit conditions.
Technology 2 fires a constant laser that deals low damage, at the cost of a halved fire rate of normal tears. Normally, this wouldn't be a problem, but since the Cathedral's boss fires a shot every time you hit it, you'll face Bullet Hell and won't be doing nearly enough to compensate.
From Wrath of the Lamb, the Mega Fetus powerup. It's a limitless version of the Doctor's Remote, which fires a missile at a target you position on the floor. You can hit anything in the room, from anywhere in the room, for the same amount of damage as a mega-bomb (thus able to blow open doors, too). It also fires fairly quickly, short enough to be viable for defense yet long enough to aim well enough once you get used to it.
To note, Epic Fetus is an item with which it is entirely possible to beat the game, having not picked up any other items whatsoever.
The Blue Candle, an item that does an incredible amount of damage, pierces enemies, destroys enemy fire, and recharges to full a few seconds after using it without requiring any other space-bar augmenting items. It can be bought from a shop as early as the first floor if you're lucky, and unless you get an even more powerful item, will stay relevant all the way to the final boss(es).
Author Avatar: In an odd sort of way, Ultra Pride can be for both Edmund and Florian.
Biblical Motifs: And a storyline, and a ton of references. Plus, The Bible itself appears as a collectible item, with the Book of Revelations as a separate item.
Black Comedy: The entire game is front-to-back, blacker-than-black Dead Baby Comedy. Power-ups include the severed body parts of beloved pets (which act as damage-ups, given that the game weaponises tears), a wire coat hangar (a home-made abortion tool which amps up Isaac's tears), and various (possibly) aborted or otherwise dead siblings of Isaac's including Brother Bobby, Sister Maggy, and Harlequin Baby (who act as combat pets). Hell, there's even a Secret Characterin the form of a cyanotic baby corpse.
The Blank: The angel (possibly God), that appears in Angel Rooms as an alternative to deals with the Devil.
Body Horror: Most powerups do horrible things to you in exchange for their effects. In no particular order, you may grow tumors, become a living insect hive, a walking CDC nightmare, cry blood, prop your eyes open with toothpicks, jam implants into your eyes, and so many more.
The battery allows you to charge up your item much faster than usual, if you stick around in combat for a while. Simply kill all but a single enemy, and dodge until you get all you can out of it.
One item allows you to restore half a heart for every 13 enemies you kill. One regenerating enemy can regenerate back from the point after they count as a kill for the purpose of this item. Like the above, it's a slow slog to max health, but there's a good chance it's worth the trouble. The same can be true when you're in the later levels and find an arcade. In fact, the more useful it is, the more boring it becomes.
The Book of Revelations is more or less this. On one hand, its only effect is to give you soul hearts (and make the Harbingers appear). On the other hand, its effect gives you soul hearts and it gives you more chances of getting Meat Boy. Depending on how how many levels you play through, you can easily get more soul hearts than you have room to display, provided you don't take too much damage.
The Candle from Wrath of the Lamb is also more or less this. It shoots a small flame forward a relatively short distance, doing very decent damage to anything it passes through, enough to One-Hit Kill most normal enemies. It also has the shortest non-zero recharge rate of any activateable item in the game, i.e. a few seconds. You don't even have to clear the room first. This makes it EXTREMELY useful against anything large, armored, or slow/immobile. Oh, and it can damage Satan's second form while it's still in statue mode while you're fighting his first form. Not as impressive as the Doctor's Remote or the Necronomicon, but still extremely useful.
The Bloody Penny trinket. It sometimes gives you a half-heart whenever you pick up a penny or other coin. While not as useful/awesome as Maggy's Faith (free eternal heart at the start of each floor) or The Polaroid (gives you an emergency protective forcefield as well as letting you into the Very Definitely Final Dungeon), those dropped hearts add up, allowing you partially farm for keys, bombs, and money in the Arcade (Blood Bank trades hearts for money; Bloody Penny gives you hearts when you get money; Slot Machines sometimes give out bombs, keys, money, and hearts in exchange for money)
Boss Bonanza: The Womb randomly has previous end-of-level bosses spawn in normal rooms. Sheol and the Cathedral have a much higher chance of these encounters. The Chest has a boss in every single room.
Many of the bosses will also make encore appearances as Degraded Bosses; sometimes two at once. The challenge rooms become this in later levels.
Taken up a notch with Wrath of the Lamb's "Curse of the Labyrinth." This Random Event basically combines two floors, meaning you'll have to fight two bosses one after the other. There's also special challenge rooms that only spawn bosses, even at earlier levels (and they spawn harder bosses in later levels); these rooms are normally accessible only if the player has one or half a heart left.
Pushed even further with The Chest, The Very Definitely Final Dungeon. To elaborate, this floor is made up entirely of rooms containing two bosses that must be fought at the same time, which definitely helps to solidify this game's Nintendo Hard status.
Brutal Bonus Level: Sheol.Wrath of the Lamb also adds The Cathedral, and, if you beat The Cathedral while carrying The Polaroid, then The Chest as well.
Bullet Hell: Things can get quite ugly with several shooting enemies on the screen.
One of the available powerups is a chunk of meat which, after collecting several, can be used to create a Meat Boy who will follow you and help fight enemies. There's an achievement for finishing him.
The walls of the Arcade are lined with posters of other McMillen games (like Time Fcuk).
Certain characters from other games make cameo appearances as alternate versions of boss fights, like Steven for Gemini, C.H.A.D. for Chub, Gish for Monstro 2, and Triachnid for Daddy Long Legs. The only alternates that aren't cameos are the plot important ones, It Lives and ???.
Dead Character Walking: It was patched out quickly, but there was a glitch in 1.3 that could do this. if you had only half a heart left aside from ???, who has no natural hearts, and take 1 heart of damage; rather than dying like normal, you would instead act as if you had constant mercy invincibility. It was as if you had book of shadows on constantly, touching or getting hit by Greed would still sap your money, but you never took damage at all, were counted at low health, and could use health taking machines, like the devil beggar or blood donation, constantly with no penalty, while technically dead. Picking up a full heart would restore you to half a natural heart.
Deal with the Devil: The Devil Rooms allow the player to exchange Max HP for items. Wrath of the Lamb introduces the demonic beggar, which damages the player in exchange for the possibility of dropping an item.
Maxing out tears in the early floors can result in this, depending on your base damage. Isaac with full tears and no damage upgrades can take down high level bosses such as Loki and Monstro II competently by swarming them with tears. Even more deadly with piercing, homing, or curving tears, or Standard Status Effects tears, whose effect chance is calculated on a per-hit basis.
The thin odd mushroom deliberately invokes this by increasing rate of fire to maximum while reducing damage.
Degraded Boss: Many bosses can reappear somewhere as a "normal" enemy.
Denial of Diagonal Attack: While it is possible to influence the angle of your tears by moving strategically, other than that you'll have to make do with just the basic cardinal directions. Whipping shots becomes impossible with Technology and Spoon Bender, and similar items have no effect on it.
The Whore of Babylon item, which makes the player much stronger when having only half a heart. Eve starts the game with this item. It's not a Desperation Attack if ??? picks up this item, as it is always active.
Cain wears an eye patch. He shoots tears only from one eye, and when he acquires an item that would go over his patched eye, it's replaced with an exclusive-to-him version.
The Common Cold replaces your tears with poisonous mucus. If you find something that replaces your tears with something else (e.g. lasers), your attacks can still poison enemies, and most such items get an additional effect. Mom's Knife, for example, drips with green poison, and most lasers turn green.
The Fetus in a Jar allows you to shoot bombs instead of tears. On one hand, it can hurt you and it takes good timing. On the other hand, you have limitless bombs, and enemies (especially bosses) die REALLY easily. This is taken Up to Eleven with the Ipecac Syrup in Wrath of the Lamb: Does more damage than bombs and poisons on hit, but its arcing path is very difficult to work with.
Distant Admiration fly. With proper skills, it can kill a boss relatively quickly.
Mom's Knife. Incredible attack power, terrible range unless you charge it (and there's no indicator of how much you've charged it, so that's basically guesswork).
The Brimstone item. It instantly upgrades your damage to maximum, can hit multiple times per shot, and ignores all terrain. The problem is that it takes a couple seconds to charge up, and it cannot be fired -at all- without being fully charged up. Moreover, it doesn't knock back enemies. However, anything which upgrades your tear fire rate shortens the charge time, and the chocolate milk item allows you to fire it without charging it up fully. It is actually a Game Breaker earlier on in the game, utterly annihilating enemies in the first few areas of the game (and if you get it with Eve, it removes her disadvantage of having a very poor initial attack rating), but it starts to become much more difficult to use in the Womb, where many enemies move and periodically become invincible, making timing shots much more difficult (and a wasted shot means you have to wait another couple seconds to try again, whereas you can simply spam tears).
A high Speed stat. Normally its hard to work with it because of the increased chance of running into hazards, but with enough practice and reflexes (and a flight item while we are at it) one can run circles around everything, sidestep bullet spreads than a slower character would be forced to weave through, and add enough momentum to tear shots to knock back enemies several feet. In fact, a well timed knockback shot can prevent a monster's shots from flying past their noses, because of the physics of shooting while moving backwards. Diagonal shots are also far easier to pull off, and at a wider angle.
Disc One Final Dungeon: The Depths 2. The Disc Two Final Dungeon, the Womb 2, was the original Very Definitely Final Dungeon. A Halloween patch added Sheol, the new Disc Three Final Dungeon. Wrath of the Lamb introduces the Necropolis 2 as an alternate Disc One Final Dungeon, and Utero 2 as an alternate Disc Two Final Dungeon. It also introduces the XL versions of these levels, which combine stages 1 and 2. A later patch turns the Cathedral into an alternate Disc Three Final Dungeon. Finally, with the Wrath of the Lamb version 1.3 patch, The Chest, gets added as the Disc Four Final Dungeon.
Double Unlock: When you manage to unlock a secret item, you're only told it now has a chance to appear in the game. You still need to find it physically to use it!
Dummied Out: The Explosive Diarrhea pill (which made Isaac drop bombs uncontrollably for a few seconds) was removed from the game because a patch broke the pill, and was unable to be re-implemented correctly.
Level 4 Meat Boy, who can only be obtained without bug-exploitation just before the start of the last level of the game. On your first ten playthroughs, at least... He will crush almost everything on that level with ease if you can stay out of the way for more than a few seconds.
You're guaranteed some of these in the the very last bonus level, The Chest, as long as you have keys — four golden chests are guaranteed in the starting room and every chest in the level has an item in it.
Elite Mooks: Each enemy type has a tougher, tinted / colored version that will almost always drop an item when killed. Different colors have different meanings, which are NOT consistent between enemies. An orange Knight won't act like Orange Chub.
The End... Or Is It?: Just as Isaac appears safe, his mother appears in the background behind him, holding a knife. One's doubt of final victory becomes apparent as all your victory means is that The Womb is unlocked and mother merely 'sleeps'...
Empty Room Until The Trap: Each level may have one specially marked room with a chest or item that, if you open/take it, will trigger three waves of enemies. Wrath of the Lamb offers a different version where you fight two degraded bosses in a row.
Evolving Weapon: The Cube of Meat, an item that only drops from The Harbinger bosses. Every cube you get increases how effective the powerup is. It also reminds one of a certain skinless boy after the second cube.
Meatboy Lvl. 5—That's what some players call the severed body "generated" by The Shears. The reason behind it is because it used to be possible to have it constantly following you by acquiring five Meat Cubes via glitch exploitation.note It's still possible to acquire more than 4 Meat Cubes, but now the fifth one you get transforms into a new rotating Meat Cube instead of upgrading your 4th Lvl. Meatboy.
Faux Horrific: At the beginning of each level, we see Isaac remembering some awful torture he has been through. In one memory, he is sitting on the toilet and notices there is no toilet paper left—but his horrified reaction is the same.
Flies Equals Evil: Flies are a very common enemy, and several other enemies vomit flies.
Freeze-Frame Bonus: Ending 13 has a hidden and hard to read message that appears for just an instant before it returns to the title screen. It reads "GET IN THE BOX!" (possibly a Shout-Out to Time Fcuk).
From Bad to Worse: One of the rewards is making the game more difficult after beating it a certain number of times.
All the endings except the first, "Epilogue". The general format is: Isaac beats Mom, goes inside her womb for two more levels, and kills Mom's Heart, which drops a giant chest. Isaac opens this chest and finds an item which will be available next game, which he is unduly excited about, and optionally something bad happens to him. Especially notable for Mind Screw is the "Everything's Terrible!" ending, where Mom's arm pops out of a chest and drags him in. Yes, her arm popped out of a chest in her own womb. No resolution of the plot from the introduction actually occurs. For that matter, the intro plot and normal ending combined make up a story that doesn't really fit with the rest of the game.
One of the items introduced in the Halloween update, Brimstone, causes Isaac to shoot enormous streams of blood from his mouth. Sounds awesome? Depending on which upgrades you get or currently have, you may end up being unable to attack at all. The boss of the level added at the same time as Brimstone was also initially immune to it due to a bug.
Another glitch from the Halloween update: The Headless Horseman would sometimes replace the boss of the new level. This wouldn't crash the game, but this would horribly distort the music and you miss out on fighting the True Final Boss.
A similar glitch to the above used to happen in Wrath of the Lamb. The Random Event "Curse of the Labyrinth" combines two floors from the same tier into an "XL" version, causing the player to have to fight two bosses, one after the other. It is possible for the Final Boss to be the first boss fought in the Depths XL (or its alternate, the Necropolis XL). Normally, when the Final Boss is defeated, it becomes impossible to leave the room, and if the boss is fought first in the XL version, then the game would not recognize the level has been completed. This left the player stuck in an inescapable room, unless he can use a teleportation item. A similar thing could happen with Mom's Heart in the Womb/Utero. Thankfully, this bug was fixed a few days later.
Not exactly game breaking, but there's the whole mess with Wrath of the Lamb's True True Final Boss. The boss screen shows ???'s image with the name "Daddy Long Legs". Previously, it was an alternate version of Daddy Long Legs, labeled in the game's files as Triachnid (a Mythology Gag to a previous game by the programmer). Currently, it's Blue Baby. This created a lot of Epileptic Trees.
The v1.3 update had a severely exploitable one. Using a Blood Donation Machine or Demon Beggar to reduce your health to zero made you completely invincible until you picked up a heart. This made the No Damage Run achievements pathetically easy. Luckily, it was patched mere hours after the update.
Get Back Here Boss: The second stage of The Mask Of Infamy (can only be hurt in the back, and it turns and zigzags very quickly). Also inverted with Lust and Super Lust, where you have to run away as fast as you can to avoid taking Collision Damage.
Glowing Eyes: Some powerups, such as Sacred Heart, cause this.
Dear Diary, Today I died. I was killed by this thing [picture of monster] in some basement/cave/dark/warm/cold place. I leave all that I own [items] to my pet cat Guppy. Goodbye cruel world -XOXO Isaac/Maggy/Cain/Judas/Samson/Eve/Blue Baby
Heart Container: These can be found here and there, although only one of them resembles a heart. Some even grant two Max HP, and/or restore all your health when you get them.
Holy Halo: With three different varieties! There's The Halo (which is exactly what it sounds like: a gold circle hovering above your head), there's Scapular (which is the older interpretation of the halo: a glowing light behind Isaac's head), and there's the Holy Grail (like the Scapular, it's a glowing light behind Isaac's head, but it's a "spikier" light. That is, it's a many-pointed star of light instead of a bright haze). Also inverted, in that there's three varieties of demon horns as well: Loki's Horns (tiny black horns Isaac wears on his head), the Pentgram (larger horns that literally grow out of his head), and Brimstone (giant, curled black ram's horns that sprout out the sides of his head)
Isaac's secret starting item. You need to beat the game's (initial) true final level ten times, which is quite a lengthy and dangerous task. And after that, you need to beat it once again with the resident Joke Character, which is nothing short of an extremely painful ordeal. But if you manage to accomplish this mission, your reward will be: Luck Manipulation Mechanic: The all-mighty D6 dice! An activated item capable of transmuting any collection related item(s) into other random item(s).
Another one shows up in the Halloween Update. Mom's Knife, which is absurdly powerful.
Invincibility Power-Up: The My Little Unicorn and the single-use Chariot tarot card both protect from and cause Collision Damage. The Gamekid powerup turns the game into a short round of Pac-Man. The Book of Shadows prevents the player from taking damage.
Joke Character: ???, unlocked by beating the true form of the game's True Final Boss 10 times. He starts with the same stats as Isaac (not even Cain or Judas's improved offensive stats) except all his hearts are soul hearts, which can't be healed like regular hearts can. He can't earn regular hearts, either; any health upgrades are converted into soul hearts. He also starts the game with The Poop, which creates a pile of poop.
Lethal Joke Character: The soul heart mechanic of the character does lend itself to some amusing exploits, though. Since Challenge Rooms check against regular hearts, he can enter them with any amount of health. The same goes for items which check against minimum health, meaning the Polaroid (temporary shield) and Whore of Babylon (Critical Status Buff) either activate every single time or are always on. Items that grant a temporary health bonus instead grant a permanent soul heart (the Liberty Cap can thus be tediously abused for functionally limitless health). The Wafer item reduces the cost of all Devil Room items to 1/2 a soul heart. By contrast, however, some items just outright do nothing because he has no actual health.
Joke Item: The Poop, which just drops a pile of dung where you're standing and can be used once per room. Maybe it can be used for cover and maybe it can be used to block an enemy chasing you, but virtually any other item is more useful in any situation.
Kaizo Trap: Due to the way Mom's attacks work, you can still be hit when you kill her. Her foot is preceded by a shadow, and if she dies while the shadow is present, the attack hits that spot instantly.
King Mook: Chub is the standout, but as of Wrath of the Lamb, the Mask of Infamy is for the Mask-Heart enemies.
The Krampus: Added as a boss in the Christmas update. The Krampus will randomly appear in the Devil room, with the chances of him showing up increasing the more you visit the room and even more if you actually take items.
The Bible grants flight for a room and doesn't recharge for another six (barring other items to increase charge time), but kills the final boss and the original two TrueFinalBosses in one use. Don't try to use it on any of the True Final Bosses added after the initial release, though. Just don't.
By extension, the Rosary has a fairly disappointing obvious effect (It just adds three soul hearts), but it can often be used to cheat the devil out of some of his nicer items without dying and has the side effect of making a Bible more likely in shops, guaranteeing an easy final boss if you get it. Plus, when playing as ???, it's a godsend.
The Nine Lives item makes it so you gain eight extra lives, at the cost of setting your max HP to one when you pick up the item and whenever you die. Normally this is a pretty lousy trade-off, but with Judas, Samson, or especiallyBlue Baby, it might very well be functionally free.
Living Apart: In later levels, enemies are encountered that are just living brains, rolling guts, or disembodied hearts.
Some of the enemies can attack the player even after losing their body or head or they just get separated.
Transcendence removes the player's body, allowing you to float over rocks, pits, spikes, and damaging liquids. One of the better items.
The Shears and the "The Hanged Man" Tarot card also do this, but only for one room. Transcendence, a noose, does it permanently. If Isaac has items that make him look demonic, on the other hand, he gets wings instead.
Every single playthrough, due to the randomized nature of the game. You can never guess if items will complement each other, or if they'll even be useful. This includes boss drops and shop inventory. Key and bomb drops can either leave you with a surplus or lock you out of chests and treasure rooms if you fall short. The good stuff in the shop costs just enough that you probably won't be able to pay for it until you've gone down three or four levels, when Greed loves to lay its ambushes. Pills are always random, and are just as often bad as good (unless you have the Lucky Foot or PHD). Slot machines and the like won't pay out half the time without good luck. Basically, there is always a chance that you will reach the end of the game with a much more or less powered up character than you expected through no fault of your own. On the extreme, it's possible to get absolutely no useful upgrades, all bonuses being activated items that you do not want, or things your character doesn't benefit from at all. On the other hand, it's possible to get an item combination that absolutely dominates everything. That said, due to the way items are unlocked, each successful playthrough means it is more likely items will be useful, and the fact that the game gets longer means more items to find. The first playthrough is often the toughest.
Acquiring 4 Cubes of Meat! It requires you to fight and kill all four Harbingers in a single playthrough. Unfortunately, there's no guarantee you'll encounter all of them in a single run, even if you acquire a Book of Revelations early on (another luck mission on itself), which increases the odds of encountering them.
Bosses also contribute to the luck-based nature of the game. Not all of them are equally difficult, and depending on a character you choose and powerups you get, some might be a cake-walk (Larry Jr., Loki, etc.) and some an endless source of frustration (Gurdy for a slow-moving character, Monstro II for people who dislike close-range combat). And since not getting hit (which is more difficult if you get a boss you are faring poorly against) is almost a requirement for getting access to the devil room, which often allows one to balance the odds, the difficulty snowballs depending on how muchRandom Number God loves (or hates) you.
Luck Stat: The original game has an item called the Lucky Foot that increases luck — which in this case means better pills, rewards from locked treasure chests, and better chances of Rewarding Vandalism and winning the skull game. Wrath of the Lamb introduces items that explicitly increase or decrease luck; it's unclear if this is related to the Lucky Foot or not.
Ludicrous Gibs: The fate of every single enemy you destroy is being turned into these.
Macrogame: Each playthrough is different than the previous one, but as achievements are unlocked, more and better items begin appearing.
In terms of items, the Wafer makes anything that hurts you do exactly one half-heart of damage. It does almost nothing for the first half of the game (where pretty much only Champion enemies, collision with bosses, and your own bombs hurts for more than that), but starting at the Womb, everything does a full heart of damage, so the wafer effectively doubles your health (and any health pickups).
Using Guppy's Paw (which trades heart containers for three soul hearts) for most of the game would be a bad idea and leave you with no hearts by the end. Holding onto Guppy's Paw and using it right before the end of the game will give you three times your max health to face the final level/boss with (you could even use it after already being damaged to make that four times).
Believe it or not, ??? as of the last update. In order to make it less luck-based to get to The Chest, Mom always drops The Polaroid when killed. Now, besides being required to access The Very Definitely Final Dungeon, the Polaroid casts a protective shield wherever you have 1/2 heart or less. ??? always has 1/2 heart or less. That's right folks, the Lethal Joke Character has the greatest life expectancy in the late game.
The Bible. It allows you to fly for a single room. While useful, there are items that grant this effect permanently and don't take up your special item slot. It also has the slowest recharge rate possible, so you only get flight once every six rooms (without upgrades). But, if you use it on Mom and Mom's Heart/It Lives, they die instantly, allowing you to bypass two of the hardest bosses in he game and making the No Damage Run in each section a lot easier. Just don't use it on the final bosses.
Malevolent Architecture: Useful items may be stuck behind rocks or pits, and in many cases it's not worth expending a bomb to get to them. In later levels, this gets more and more common, in addition to rooms being laid out to make attacking enemies more difficult (and them attacking you easier) and eventually adding random spikes.
Meaningful Name: The Wrath of the Lamb expansion's name foreshadows two of the bosses introduced in the game (i.e., a Messianic Archetype version of our main character, and one of his alter egos).
Mundane Made Awesome: After everything that just happened, Isaac gets rather surprisingly excited over the items in the endgame chest, including a hat, a nail, a quarter, a fetus in a jar, a wafer, and some bling.
Name of Cain: One of the unlockable characters, not surprisingly considering all of them have Biblical names. While not outright evil, Cain is somewhat shady-seeming — he wears an Eyepatch of Power and his abilities make him resemble a "rogue" class.
Nintendo Hard: No continues. You start with one life and additional lives are very, very unlikely to show up once along multiple playthroughs, much less a single one. If you die, you start all over again. The configurations of rooms and upgrades are randomized, and in some situations damage will be unavoidable. Survival depends on reflexes and calculated risk.
And Wrath of the Lamb takes this even further! If you thought the vanilla version was merciless, you won't survive the new horrors you'll face here. Good thing you also get new (and awesome!) power-ups to help you compensate for the difficulty boost.
No Cutscene Inventory Inertia: No matter what the player has picked up, the character at the cutscenes is still what he was at the beginning. For that matter, it'll still be Isaac no matter which character you're playing as. Although, considering the achievements imply most of the characters are Isaac wearing a Paper-Thin Disguise of some sort, it may be fitting after all.
No Damage Run: A no damage run of each area will earn you a Steam Achievement. It's also enforced with at least two characters in different ways.
No Ontological Inertia: Averted; any flunkies spawned by a boss will not die when the boss does (except in the case of Mom) and must be killed in order to clear the boss room.
One-Hit-Point Wonder: If you take a Devil Room item without having the regular hearts to pay for it, but still have soul hearts when you do, Isaac is reduced to zero health (no hearts or soul hearts) and will die from a single hit. Any health upgrades you collect instead pay off the debt, after which they can be acquired normally. You can, however, collect more soul hearts for a buffer.
One-Winged Angel: The Nail (unlockable after one of the post-Mom's Heart endings) allows Isaac himself to use this trope for the duration of a room each time it's charged. The Whore of Babylon curse does it as well, triggering when you reach low health.
Ouija Board: Serves as a power-up that gives Isaac ghost tears that move through objects.
Palette Swap: Enemies with a different color palette. They're stronger but drop items upon death.
Paper-Thin Disguise: It's heavily implied that the unlockable characters are just Isaac wearing these.
Poison Mushroom: The Tick, a randomly spawning trinket that makes bosses start out at anywhere from 5 to 15% less health from full, is fairly useful. What makes it bad is that it latches onto you and can't be removed by anything, making the negatives of it far outweigh the positives, and since the the Polaroid is needed to reach The Chest, picking the Tick up by accident when you can't find or buy mom's purse basically makes the game Unwinnable by Design.
Potty Failure: The item "Lemon Mishap" allows you to lay down a puddle of pee that damages enemies, and the item "Number One" replaces your tears with a rapid-fire stream of urine. Also, certain pills will give you bad gas or literally explosive diarrhea. There's also the boss monster Peep, who uses urine as his main weapon.
Critical Annoyance: Isaac leaves puddles of urine every room he enters when he is down to his last hit point.
Purposefully Overpowered: The Wrath of the Lamb expansion adds a lot of incredibly powerful new items and effects that would be extremely abusive on the vanilla version of the game;note Some of them, for example, combine the effects of two already powerful pick-ups, in a single item! You'll need every one of them if you want a chance to survive (not win, just survive!) the horrors you'll find on the new floors.
The dead cat item. You have eight extra lives, yes. You also have your health bar reduced to one heart (and any health bar increases you find vanish on respawn), and if you die you respawn outside (with your secondary item still used up if you used it and any Faith Hearts still gone) and enemies fully heal. So good luck beating any bosses you couldn't kill on the first try. And those eight extra lives are going to need to last you the entire rest of the game.
Also My Reflection, which turns all your shots into boomerangs that follow you. These have abysmal range (and any range pickups you get make them boomerang further, which is pretty much useless) and behave in goofy ways which can be hard to predict or keep track of because they follow you rather than a trajectory. They could theoretically be useful, but you'll probably just get hit more by having to think about them.
A high speed stat, as well. You'd think it'd be useful, but once you get four or five, it becomes very difficult to control the character and prevent yourself from careening into spikes, monsters, fires, shots, etc. Less obvious/problematic with flight.
Samson, a character added in Wrath of the Lamb, is basically Judas... but with a lower base attack. (He is skilled at fighting mobs of enemies, but that's not much consolation if you have to fight one of the few bosses that doesn't summon punching bags.)
Any item that either conflicts severely with items you already have (Mom's Knife after finding a Fetus item, for example), do not benefit your character at all (Yum Hearts for ???, anyone?), or is an activated item found after finding your activated item of choice.
Guppy. While the ability to fly and spawn blue flies is pretty good, it requires a three item combo; one of these may need to be the above-mentioned Dead Cat, and you'll almost definitely need to trade in some health in a Devil Room for it. In comparison, the three item combo of Wafer+Habit+Yum Heart/Book of Revelations/The Nail makes you functionally invincible for the entire game, and there are two item combos that are significantly more powerful than Guppy.
Random Event: The Curses introduced in Wrath of the Lamb, which are randomly activated at the beginning of a level. Curse of Darkness makes the map useless, while Curse of the Lost increases the size of a floor from what it would normally be and removes the pattern for Secret Room spawning. Curse of the Labyrinth combines two floors of the same tier—including two item rooms and two bosses.
Reset Button: Forget Me Now, an item unlocked by defeating Satan with ???. It starts you over from the beginning of the current level with a new layout and new monsters, including the boss. Why would you want to use this? The reset level also has new items, giving you more opportunities to power up your character. The only problem is that Forget Me Now is a one time use spacebar item, forcing you to abandon your current spacebar item and beginning the reset level with that item slot empty.
Revive Kills Zombie: The Bible, while normally dealing no damage, kills Mom and Mom's Heart instantly.
Rewarding Vandalism: Rarely, destroying poop and putting out fires drops an item. Rocks with a small X on them (usually identifiable by their blue-tinted color) will also drop an item when bombed. (Destroying lots of poop this way unlocks The Bean, and blowing up enough rocks unlocks The Small Rock.) And then there's the secret rooms, which are revealed by blowing up walls.
Roguelike: Things like level layouts, monsters, items, and most bosses are randomly generated — though it's also level dependent (i.e. you will never find a Caves boss in the Basement, unless the boss could appear in both). Wrath of the Lamb even randomizes what level you'll be sent to by providing alternate stages. For example, in the original version, the first two levels would always be the Basement. After the expansion, each of the first two levels will be either the Basement or the Cellar.
Save Scumming: Because the game is randomized, you can instead do this on startup to get preferential powerups instead of garbage (the latter being more likely).
Scare Chord: Played on certain endings and when you enter the Devil Room.
Secret Character: ???, who is actually Dead Baby from one of Edmund Mcmillen's earlier works.
Self-Deprecation: The creators of the game appear as a rare variant of one of the Seven Deadly Sins. Namely, the the butt-ugly Ultra Pride, due to a feeling of pride and satisfaction at finishing their game.
Self-Imposed Challenge: Pretty much the only reason why anyone would pick up the nine lives item (which reduces your hearts to only one and resets them to one every time you die) willingly outside of 100% Completion, the challenge of the same name, or turning one of the characters into Guppy.
It's possible to reach Sheol without beating the game ten times either by using the "We Need To Go Deeper" item or taking the hatch in the (possible) Devil Room in the supposedly last stage.
While it might be a bug, it's currently possible to get credit for beating the game as ??? long before you can even unlock him...by using The Ankh, an item that gives you an extra life, at the cost of transforming into ??? on respawn. Considering you can't unlock the character until you've beaten the (constantly growing and changing) game 10 times, finding this particular item, and getting to the final boss, and then dying to respawn can save you a LOT of time and trouble, as you keep most other powerups when you come back... meaning you don't have to play a full game with what is essentially a joke character to unlock a powerful item for Isaac.
Serial Escalation: This game has issues with one-upping its own final dungeons every couple of patches.
Set Bonus: As noted in Ascended Extra, acquiring 3 out of 4 specific cat-related itemsnote these being Guppy's Tail, Guppy's Head, Guppy's Paw and Dead Cat. in a single playthrough will transform Isaac into his deceased cat, Guppy. Not only does it make you look hilarious / adorable, but it grants you the abilities to fly and spawn blue flies whenever you hit enemies.
Seven Deadly Sins: Personifications of these are present in this game as minibosses. Beating all seven unlocks a new item. Super versions appear in Wrath of the Lamb.
Smart Bomb: The Death tarot card, the Necronomicon, and one of the functions of the Sun tarot card.
Skeleton Key: Gives 99 regular keys, which is probably all you'll need and then some. A straighter example appears in Wrath of the Lamb with the Golden Key, which allows you to open any door in the floor where you get it without spending any of your Interchangeable Antimatter Keys, then vanishes after the floor is exited.
Sorting Algorithm of Weapon Effectiveness: For the most part, items unlocked later aren't any more powerful than those at the beginning... except the familiars, where the ones available at the start fire vanilla bullets and those acquired later have much more exotic and useful attacks. And the health-increasing items, where the unlockable ones generally either heal you or give you some soul hearts as a bonus.
Spiteful A.I.: The algorithm for determining in which shops does Greed spawn is overly complicated for what in practice boils down to "Could the player afford an item in this floor? If so, spawn Greed. Does the player own an item powered by coins? Drop a shop in every shop."
Some players say that the game has a "troll engine" that manipulates the random drops you get just to laugh in your face, especially if you tempt fate by grumbling about never having enough money for shops, and then the game gives you a Steam Sale (half-off everything in the shops) right after you've fought Greed in the very last shop in the game.
Stealth Pun: The item "Mom's Eye" makes your tears fire in two directions at once — in other words, Mom really did have an eye in the back of her head!
Standard Status Effects: Paralysis, slowdown, poison. Interesting case, since only Isaac gets to inflict them on enemies (with the exception of the Death boss).
Your reusable item can only be replaced with a different one, though depending on the character, you might start out empty handed. Likewise, you can only drop a one time use item by picking up a different one, which can be stressful if you end up holding one you know would be detrimental to your health if you accidentally used it.
Wrath of the Lamb adds trinkets, which can only be exchanged if you find another one. Trinkets are passive abilities, so this usually isn't a problem — but there is actually one trinket that cannot be removed no matter what. This is not a bug, although it is a literal bug; the trinket in question is a Tick. Ticks are hard to remove!
Even worse, since the Tick can't be removed, this prevents you from picking up the Polaroid, a trinket needed to access the Very Definitely Final Dungeon.
Take Your Time: There is no time limit of any kind, and you can backtrack as much as you want within a floor.
Tears of Fear: Isaac's default mode, given his crapsack childhood of abuse, harassment, and attempted filicide. When Isaac picks up a demonic upgrade, these frequently become Berserker Tears. Other upgrades or items give him Tears of Blood. And when he gets the 3 Dollar Bill, he gets Tears of Joy.
Teeth Flying: The Tough Love item, appearing visually as brass knuckles, allows Isaac to randomly spit teeth instead of tears. If Isaac has items which increase the visual size of his tears, he'll also shoot larger teeth.
Too Awesome to Use: Some of the Tarot cards and the Full Health pill, usable only once. Possibly some of the more powerful subweapons which can only be used once every six rooms. The epitome is the Sun Tarot Card. It is a full health pill, Necronomicon, and one-floor Compass and Treasure map, all rolled into one. It's agonising deciding whether to use the card to see all a level has to offer, or save it for emergencies or for the final boss.
Turns Red: All four of the Harbingers, Gemini, Peep to a minor extent, Carrion Queen, and Mom's Heart. Some are actually less difficult after turning red.
True Final Boss: Mom's Heart. It Lives (yes, that's its name) is an Even Truer Final Boss replacing the True Final Boss... at least until the Halloween update came, in which Satan became the Ultimate Boss of the game. If you thought this was already turned Up to Eleven, Wrath of the Lamb introduces an alternate floor for Sheol, making ANOTHER TRUE FINAL BOSS.It's Isaac. And there's YET ANOTHER ONE if you beat him while holding the Polaroid, requiring you to traverse the we promise this is the last Very Definitely Final Dungeon full of bosses and nothing but.
Underground Monkey: In both new model and palette swap flavor. Even a few bosses come in variants, some of which being Shout Outs to other games.
Thanks to a teleportation item (either pills or the Teleport! item) and some rotten luck, a player can find themselves stuck behind a room full of rocks, with no bombs to break them, making it impossible to continue, and forcing them to quit out of their current run.
It happened to the game author himself. In his co-commentary with Northernlion, he mentions that, after getting a certain combination of power-ups and power-downs, his firing range was too low to reach some monsters standing behind a pit — and killing all enemies is required to leave a room.
The Wrath Of The Lamb expansion has issues with this, with XL levels being the main culprit. The player may teleport into an area with no exits, or the game may not spawn the hatch to the next level if certain bosses are fought first in the Sequential Boss fight.
Wrath Of The Lamb also adds a challenge run reel, one of which is called the purist. The point is that you have to defeat the Disc Three final boss without access to item rooms. The game forces you to go up to the Disc Three Final Floor by having no trapdoor to the other Disc Three Final Floor, only a beam of light that takes you to where the challenge wants you to go. However, if you, by any means, manage to teleport yourself out of the beam of light before the new level loads, the beam will disappear from the boss room and you'll be permanently stuck on the Womb/Utero 2 with no means to get out.
Luck-Based Mission: a new character, the Mystery Man, is entirely built around this trope, starting with random stats and items. However, using it requires "tokens", which are acquired by beating Mom without the Mystery Man.
Retraux: Rebirth's art style is intended to resemble a colorized Gameboy game.