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- Superman archnemesis Metallo. Uranium capsules will sustain his robot body for a short time but kryptonite will sustain it indefinitely. Carrying around Superman's weakness in his chest is just icing on the cake.
- Ultraman, the version from the anti-matter universe that's an evil counterpart to Superman, requires periodic exposure to Anti Kryptonite to maintain his powers. Its unclear whether it simply keeps him powered or keeps him alive. He seems to be in bad shape without it but he's also fighting Martian Manhunter at the time.
- Parasite is on a strict diet of the life force of living creatures. Superman is a giant buffet for him.
- In some depictions, Batman nemesis Clayface requires treatments to keep his body from dissolving. Regardless of the situation, he's always looking for something to give him better control of his form.
- In the recent Green Lantern titles Sodam Yat must now permanently wear a power ring, despite being the bearer of the Ion, to keep him from dying of lead poisoning he received at the hands of Superboy Prime.
- Likewise, bearers of the red power rings will die if their rings are removed, because the red light replaces their blood with its energy. Only a Blue Lantern can purge it from their bodies.
- In Daniel Clowes' Captain America parody The Battlin' American, the super syrum is extremely addictive, causing heroin-like withdrawal symptoms.
- For much of his history, Iron Man has needed to wear his armor's chest plate to keep his heart beating. In the early days, he had to recharge it regularly to prevent a heart attack. Over the years, various procedures have cured the necessity only to have some new condition once again force dependence on his armor.
- Iron Man: Tony Stark needs to keep his electromagnet on so that shrapnel in his chest won't migrate to his heart. Said electromagnet is powered by palladium. JARVIS even lampshades the irony of the situation. In the sequel he creates a new element to replace the palladium. In the third movie however the pieces of shrapnel are finally remove so he won't need it anymore.
- In the Plague Year Series by Jeff Carlson, a deadly nanotech has covered the planet and exists everywhere below 10,000ft in elevation. To be able to freely walk below 10,000 ft, someone must have a corresponding "vaccine" nano. Unfortunately, the original nano will never go away, so it and the vaccine nano are now permanent facts of life.
- In Dune, nearly all humans have been consuming spice for over 10,000 years and have become addicted to it in more ways than one. The Fremen are the most addicted, as spice is present in the very air on Arrakis, which is shown by their "blue-within-blue" eyes.
- Society itself has become dependent on spice. Even people who don't directly consume it depend on it because spice imbibing Guild Navigators are the only reliable means of navigating faster than light travel.
- House Harkonnen also makes a point of poisoning all of the captured Mentat Thufir Hawat's food, then giving him the antidote later to keep him from betraying them.
- The Guild Navigators are the ultimate expression of this trope in the Dune universe. While most humans can become dependent on it to the point where withdrawal can be fatal, Navigators are so saturated and mutated by the spice that they require it in gaseous form constantly to even breathe.
- The dinosaurs in Jurassic Park are engineered not to produce lysine, requiring humans to administer it. Pity nobody told the engineers that no vertebrates known to man do it either, and we all still survive. The book and sequels realize this and show how well it worked — i.e. not at all.
- In Michael Moorcock's The Elric Saga, the hero is an otherwise sickly and weak albino who needs exotic drugs or the dread sword Stormbringer to live. While he realises possession of the Sword negates his needs for the drug, he is sickened at the price it exacts. In one story, the villain Yyrkoon keeps him prisoner and withholds both the drugs and access to the Sword for the sheer pleasure of watching his nemesis sicken and die.
Live Action TV
- Stargate SG-1 has many examples:
- A Goa'uld symbiote provides a Jaffa with great health and stamina, as well as regenerative powers, but at puberty the Jaffa become incapable of living without these symbiotes for more than a few hours; it acts as their immune system.
- Tretonin, a chemical used to remedy the Jaffa's dependence on the Goa'uld for survival. (And made from ground-up symbiotes, at least until they figured out how to make a synthetic version.) Tretonin can also be used by regular humans (that's what the Pangarans originally developed it for), but causes the same side effects of completely replacing the natural immune system and thus making anyone who takes it unable to live without it. For the Jaffa who already lack a natural immune system, this is of course a non-issue.
- The Ilempiri were incapable of being used as hosts by the Goa'uld, so they were fed a highly addictive drug that only the Goa'uld could manufacture, until the entire species was addicted.
- The title character of the Sci-Fi Channel's The Invisible Man series needed periodic injections, to keep him from going Ax-Crazy from the Quicksilver in his system. In the Series Finale he's given a permanent cure to the insanity problem. This flaw is deliberately introduced by the Big Bad to keep his buyers dependent on him.
- Paul Turner on Strange World was pressured to work as a double agent in exchange for a serum that would keep his aplastic anemia in remission. Subverted when it turned out it wasn't the serum that was responsible.
- The Jem'Hadar of Star Trek: Deep Space Nine are addicted to the substance Ketracel White, to keep them loyal to the Founders. While most Jem'Hadar are innately loyal to the Founders anyway (on account of being programmed to consider them gods), the Founders were Genre Savvy enough to include a failsafe. It provides all the sustenance they need to survive, removing the need to eat or drink, but they also can't take nourishment from any other source. Depriving a Jem'Hadar of the White causes them to go violently insane and then drop dead. There are a few very rare mutants who don't need the White, but in general even they don't know it.
- Played with in Symbiosis, a first season episode of Star Trek: The Next Generation. The Ornarans contracted a plague two hundred years earlier, and believe they need continued "treatments" provided by the Brekkians to stay alive. Upon witnessing two Ornarans receiving a "treatment", Dr. Crusher instantly realizes that the "treatment" is actually a narcotic; the plague is long gone, but the Ornarans find withdrawal so traumatic that they're sure that they're still sick - not to mention that the drugs are making them so stupid they can no longer effectively perform basic maintenance on their ships, let along think clearly about the plague. The Brekkians are fully aware of this, but no longer need to work as long as they can trade the "treatments" for Ornaran goods. While the Prime Directive forbids Picard from revealing the truth to the wronged race, he finds a way to correct the situation by refusing repairs to their few remaining ships. Without the ships, they will have no way to get the "treatments" and will eventually realize they're not actually sick. Of course, the Brekkians are going to have an economic holocaust, but after two centuries of enslaving the other world with needles to the point that they're no longer coherent enough to repair their own ships, you might call it Laser-Guided Karma.
- In Lexx, Divine Assassin Kai needs protoblood the blood of an Insect to maintain his undead existence. It stops being an issue after the first season when the crew manages to get a good supply of protoblood.
- In the Ravenloft campaign setting, Ivan Dilisnya uses poison to keep his henchmen loyal, dosing them with a toxin called Borrowed Time. Once exposed, they'll die if he doesn't provide regular doses of this substance, which only he knows how to concoct.
- Warhammer fantasy: The elven High Mage Teclis is the single most wise and powerful magic user in the world, but his body is so weak he needs to be constantly fed healing potions to keep his heart beating.
- Rifts has the odd example of Juicers. The chemicals that give them their superhuman qualities will also kill them in a maximum of seven years (and kill them so badly that even a god can't bring them back from the dead - their bodies are completely burned out). But going off the chemicals is a horrible ordeal, so much so that most Juicers would rather die when their time's up than even consider stopping. The chems will kill them, but they can't live without them.
- In BioShock, people taking ADAM will go insane if they do it too often... and if they stop after that, there's a good chance it'll kill them. And worse still, Rapture's various businesses used it for almost everything, from sport to cosmetic surgery- up until people started going crazy and attacking other citizens for their ADAM.
- Templars in the Dragon Age series develop Lyrium addiction over time, officially, because their Anti-Magic powers run on it. Unofficially, it's pretty clear that the Chantry hooks them up on Lyrium on purpose to keep them on a short leash.
- In Deus Ex: Human Revolution, all augmented humans (with the exception of the main character) must take Neuropozyne regularly. Otherwise, their body rejects the augments, the results are... not fun.
- Of course, the side effects of Neuropozyne are not a lot of fun either: psychosis, mental degradation, and phobia are just the tip of the iceberg.
- Lest you think this merely sci-fi mumbo jumbo, many Real Life recipients of organ transplants need to do this too.
- The entire plot is kicked off by a breakthrough thanks to the protagonist's unique genetic structure due to gene therapy experiments performed on him when he was a baby that could remove the need for Neuropozyne and the Illuminati's attempt to suppress it.
- The Fallout games are full of a wide assortment of Fantastic Drugs (and mundane ones), any of which can potentially become addictive after only a couple of uses, with the withdrawal symptoms causing stat debuffs whenever you aren't on the drug in question. Luckily, it's pretty straightforward for any doctor to rid you of your addictions (and in Fallout: New Vegas there's a consumable item that does it for you).
- In Borderlands 2, we discover that some Sirens can enhance their natural powers with Eridium. However, if they use too much, they eventually become dependent. Thankfully, it seems like they have to take a lot to reach that point. As in, having it pumped into their systems constantly over a period of years.
- Dead Rising 2 introduces Zombrex, a medication that, if taken daily, will hold off transformation into a zombie. Originally it was only good for twelve hours, but in the three years between Case Zero and the game proper, they improved it. Several major characters rely on it, including Frank West. In the third game, the main character Nick is bitten partway through the game and resigns himself to his fate when he can't find any Zombrex. Only to discover that he's The Immune since Carlito inoculated him with the cure to zombification as a failsafe to prevent his Zombie Apocalypse from wiping out humanity entirely.
- The Mordesh of WildStar require regular doses of Vitalus to keep the Contagion at bay. Without it, their bodies rot away and their minds deteriorate, turning them into raving, cannibalistic monsters.
- A plot point in Resident Evil 5. Albert Wesker gained potent physical abilities after being impaled by a Tyrant in the first game thanks to his earlier exposure to the Progenitor Virus in his youth and another cocktail of viruses he ingested moments before his "death". He requires regular and precise doses of the viral cocktail to keep his mind and body stable. The heroes overpower him in the penultimate boss battle by giving him an overdose, triggering a Villainous Breakdown.
- In Endless Legend the Broken Lords are were once mortal humans who converted themselves into Energy Being's to survive the long winters of Auriga. However they now become dependent on Dust to sustain themselves, the other alternatives is for them to drain the life force of other living beings.
- The Blood Elves of World of Warcraft are completely dependent on magic since the Sunwell was corrupted by the Scourge.
- Cybersix was designed so that she requires "Sustenance" in order to live. With the only source of Sustenance being the man who created her, she is forced to extract it from the creatures that he sends to destroy her.
- What would you need with a complex organic molecule, acidic hydroxide and an oxidiser? Why, you must eat sugar, drink water and breathe oxygen to live. All three, in inappropriate concentrations and/or locations, can be deadly. (Excess free water can lyse cells, to say nothing of water shifting to places it shouldn't, as in pulmonary edema; oxygen can cause free radical damage to tissues, and oxygen toxicity is heavily implicated in retinopathy of prematurity; and either too little or too much circulating glucose—known more prosaically as diabetes—can cause metabolic derangements leading to irreversible brain damage, coma and death.)
- Long term alcohol addicts might find that withdrawing cold turkey can kill them through shock. A theoretical possibility of death also exists with benzodiazepines and barbiturates, because withdrawal from them can cause seizures, but alcohol withdrawal is the only withdrawal syndrome known to have actually killed anyone.