* ''Any'' scene involving Murray the Talking Skull.
** "If I could just get my hands on that gunner! If I could just get my hands, period..."
** "I'm not bald! I just have a really high widows peak."
** "Could you pick me up, so I can bite you?" - "No!" - "I just thought I'd ask."
** Especially this exchange:
-->'''Murray:''' I am a powerful demonic force, I am the harbinger of your doom, and the forces of darkness shall applaud me as I stride through the gates of Hell, carrying your head on a pike!
-->'''Guybrush:''' ''Stride?''
-->'''Murray:''' ALRIGHT THEN, ''ROLL!'' ''ROLL'' THROUGH THE GATES OF HELL! Must you take the fun out of everything?
* When Guybrush turns Elaine back to normal, he forgot she was about to punch him before...
* The scene that plays after you put the lice on the comb.
-->'''Haggis:''' Sure as 'am standin here, they wriggle about ye scalp like a pack o' wretched sea lions!
-->'''Guybrush:''' Good analogy.
* "[[http://www.youtube.com/watch?v=I4nJNaQIrsc I choose the banjo!]]"
* Any instance where Guybrush uses the ventriloquism book to throw his voice in Part II, but of particular note is when he uses it on the monkey pirate captain and does a [[Series/StarTrekTheOriginalSeries Captain Kirk]] impression:
-->'''Guybrush:''' (''as [=LeChimp=]'') I mean, take a look around, at me, at the rest of the crew... we're all monkeys.\\
'''Mr. Fossey:''' You mean in the Darwinian sense, sir?\\
'''Guybrush:''' No, I mean in the ''quite literal'' sense.
* The reveal that Mr. Fossey's captain is [[BaitAndSwitch not LeChuck but LeChimp]], a mute, dopey looking gorilla modeled after Captain Kirk.
-->'''Guybrush:''' But If the captain is a gorilla, then that must mean [[TheManBehindTheMan Mr. Fossey is...]]\\
'''Mr. Fossey:''' Aye aye, sir! Free bananas for ''the whole crew!''\\
'''Guybrush:''' (''deadpan'') [[BaitAndSwitchComment ...an utter loon.]]
* "MADRE DE DIOS! ES [[http://www.youtube.com/watch?v=E28WrhpTzQA EL POLLO DIABLO!]]"
** [[GratuitousSpanish "Si! He dejado en libertad los prisioneros y ahora vengo por tis!"]]
* The pirate song in Chapter 3.
** [[http://www.youtube.com/watch?v=1-9my0tsutw "We'll surely avoid scurvy if we all eat an orange."]]
* Mixing hangover medicine with alcohol:
-->''(Drink begins to bubble and change color.)''\\
'''Guybrush:''' That makes the drink oh-so-much-more appealing. ''(turns to the camera)'' [[BreakingTheFourthWall It just occurred to me that mixing medicine and alcohol is a really stupid and possibly lethal thing to do]]. [[DontTryThisAtHome If I were a real person instead of a loveably inept cartoon character with the potential for a few more sequels... I wouldn't even consider it.]] Skoal! ''(downs the beverage)'' That's odd. It's supposed to cause drowsiness. I don't feel the least bit drowsy. ''(the scene goes on a trippy InterfaceScrew)'' In fact, I... ''(his voice goes into sleepy slow motion)'' ...in fact I feel... I feel...\\
''(He chokes and falls to the floor with a thud.)''
* In the sequence where Guybrush fakes his death a ''second'' time to get buried in the Goodsoup crypt, hotel manager Griswold Goodsoup offers this gem:
-->'''Griswold''': Oh, dear! He's had a sudden and completely unexpected relapse of death!
* "You fool! You've given cheese to a lactose-intolerant volcano god!"
* On that note, Lemonhead in general. "Shut up. Or I'll eat you."
-->'''Guybrush''': Did I say "cannibal?" I, I meant to say... err, "cannon... ball." I want to be a cannon ball. BOOOOOM!
-->'''Lemonhead''': ...You're not quite stable, are you?
* Similarly, after the "human sacrifice" to the volcano god (which is actually a dummy made out of fruit), complete with dramatic ritual-saying and rope-cutting, the cannibals stand around the volcano's edge and toast marshmallows.
* The "terrifying" shape of Skull Island.
-->'''Guybrush:''' That's a '''duck'''!
-->'''Lost Welshman:''' What are you talking about? Can't you see the ''skull''?
-->'''Guybrush:''' This island doesn't look like a skull at all. It looks like a great big enormous duck. It should be called Duck Island!
-->'''Lost Welshman:''' Well, ya see... ya gotta squint and sorta turn your head and... ooooooooh! It's just ''so'' scary!
-->'''Guybrush:''' If you squint and turn your head it looks like a bunny.
* Asking [=LeChuck=] what the ''real'' secret of Monkey Island is.
* Stan's triumphant return. Especially if you've played the preceding games.
* "I'm runnin' guns!"
* Guybrush bypassing a WalkThePlank ordered by Mr. Fossey
-->'''Mr. Fossey:''' That's weird, there was no splash...
-->'''Guybrush:''' ''(from a safe spot)'' Um, [[SayingSoundEffectsOutLoud splash]]!
-->'''Mr. Fossey:''' [[WhatAnIdiot Oh.]]
* [[GettingCrapPastTheRadar Sticking glue]] [[DoesThisRemindYouOfAnything onto Murray's hand]] and attempting to give it back to him.
-->'''Murray:''' Get away from me, you sick freak!
* The fact that Stan has somehow managed to have business cards laminated despite having been locked in a coffin.
* Reuniting Charles and Minnie in Chapter 4 leads to the most (intentionally) ClicheStorm courtship display this side of the 17th century, complete with cheesy ''GoneWithTheWind''-style background music, [[ChewingTheScenery overdone dialogue with southern accents]], and the stone angel in the background looking on in shock. It's kind of heartwarming too, [[TogetherInDeath given their situation]].
* Using the "[[RunningGag Look behind you, a three-headed monkey!]]" line on Madame Xima when swiping her tarot cards.
-->'''Xima:''' *gasps and spins around* Then the prophecies have come true!
** Madame Xima in general. She takes her psychic profession very seriously, and Guybrush loves toying with her. Such as their first meeting:
--> '''Xima:''' ''[Not seeing Guybrush]'' I feel a dark presence coming over me!
--> '''Guybrush:''' Hi there!
--> '''Xima:''' ''[[ScreamingWoman AHHHHHHHHHHHH!!!!]]''
--> '''Hungover!Griswold:''' ''STOP SHOUTING!''
* When entering Skull Island, Guybrush has the option of saying the out of nowhere line to King Andre: "Your EvilPlan will never work." Andre's reply: "But it is flawless. A series of carefully placed charges throughout Blood Island, all controlled by a series of satellites in Geo-sycnronis orbit, and only one man has the master switch. I am that man, Mr. Threepwood, and I --" and by that point he's cut off by Cruff, who has been trying to get him to not blurt out his EvilPlan for no reason the whole time.
* Wally's fake beard.
--> '''Wally:''' Actually, it's a highly sophisticated beard weave made from the chest and back hair of real pirates!
--> ''[[[{{Squick}} Guybrush grimaces]]]''
--> '''Wally:''' I'm hoping it'll take root if i don't wash it for a while!
* [[TheDevTeamThinksOfEverything Performing certain actions on various people and objects]] can yield funny results.
--> ''Lick pin.''
--> '''Guybrush:''' No, I have a very low threshold for pain.

--> ''Pick up hideous pirate.''
--> '''Guybrush:''' I don't think he's interested.

--> ''Give ipecac flower to Edward Van Helgen.''
--> '''Edward:''' I'm not in the mood to ride the porcelain bus.
--> '''Guybrush:''' [[WhyDidItHaveToBeSnakes Oooh,]] [[AbsurdPhobia porcelain...]]
* Trying to cross the [[AgonyOfTheFeet Brimstone Beach]], then watching Guybrush skip back into the shade while crying "Aah!" "Ouch!" "Hot!".
* Cutthroat Bill tells you a story about his former captain, who had the ability to [[SuperSenses sense treasure.]] They sailed out of Plunder Island without a map, and spent several weeks going in circles, until the captain realized that the crew's gold coins, earrings and belt buckles were distracting him. He told his crew to throw all of their loot into the ocean. They continued sailing for two years without any luck, but when they returned to Plunder Island, they finally found treasure right off the coast. It was a pile of gold coins, earrings and belt buckles.
* Reading the tourist information sign next to the thorny plant in the quicksand pit reveals it to be a Papapishu bush, the name coming from a native word meaning "yowch". From that point on, any time any character would utter the word "yowch" in regular dialogue, they will instead exclaim "papapishu!"
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