* The "interactive" dildo in [[https://www.youtube.com/watch?v=G_PwUHGjJzU this video]].
** '''Duke:''' ''You wanna touch it, don't you?''
* Upon seeing a giant three-breasted alien monstrosity, most people would probably run and hide. Duke's response?
-->"[[ExtremeOmnisexual Hell, I'd still hit it.]]"
* Duke engages in a little LampshadeHanging:
-->'''Twin:''' "What about the game, Duke? Was it any good?"
-->'''Duke:''' "Yeah, but after 12 fucking years it should be."
* When Gearbox had to delay the game ''[[HistoryRepeats again]]'' by one month, to June 10th in Europe and June 14th in the US, Gearbox released [[https://www.youtube.com/watch?v=G6fFKkmIrWM this video]] announcing the delay, with the {{Tagline}} [[{{Pun}} "Duke never comes early."]]
* [[https://www.youtube.com/watch?v=tRBfzoqOZcs This]] new trailer really puts strain on the definition of "Mature humor"
-->'''Duke:''' ''Combo!'' ''Double Combo!'' ''Triple Combo!'' ''Super Combo!''
** And yes, there's an achievement/trophy tied into finding and stealing a piece of poo. Behold, [[http://www.xbox360achievements.org/game/duke-nukem-forever/achievement/53792-Turd-Burglar.html the Turd Burglar.]]
* During a point in the demo, Duke is allowed to draw a 'plan' on a whiteboard for some soldiers. No matter how nonsensical a drawing you make or how much of the original plan you replace, the soldier observing will respond with amazement.
-->'''Soldier:''' Why didn't we think of that!? '''WHHHHHYYYYYYYYY!?'''
** Alternately:
-->'''Soldier:''' Oh, ''man''! That is... I mean, I don't understand ''any of it'', but I bet if I did, that guy over there would still have his arm. And at least one of his balls.
* Running an enemy over with Duke's monster truck:
--> Beep beep, motherfucker!
--> Frickin' jaywalkers.
--> So much for anti-lock brakes.
* When Duke gets shrunk by a trap in "The Lady Killer" he meets a kid who says he's "the coolest toy ever." Duke's response?
-->"I'm not a toy, kid. I'm an ''action figure''!"
* Later, while shrunk, Duke ends up fighting some rats who mistake him for an easy meal.
-->"Now those were some [[Film/ThePrincessBride rodents of unusual size]]."
* Later in that chapter, Mc Ready berates Clarke for saying "Let's do some damage!". Clarke then comes up with "Let's rupture some spleens!". Mc Ready's reaction is a dumbfounded "Why are you such a douche?
** This is one of the few lines the italian dub improved:
-->'''Mc Ready:''' (''exasperated'') ''Why'' are you such an ''asshole''?
* Hearing shrunken Duke exclaim "Motherfucker!!!" in his squeaky voice as he falls down an air vent.
** Upon being first shrunk; "The ''fuck''...?"
* The text on the loading screen offers some hilarious commentary as well.
-->[[CaptainObvious When getting shot at, avoid bullets.]]
-->If you get stuck, you can always cheat by reading an online FAQ.
-->[[WhatCouldHaveBeen Picking up a turd in a toilet won't lower Ego, but we really wanted it to.]]
-->You can slap our wall boobs, since real girls don't like it when you slap theirs.
-->If you died from falling off a high ledge, [[TakeThatAudience it's probably your own fault.]]
* For the Interactive Achievement 2011 Awards, Gearbox made [[https://www.youtube.com/watch?v=-nVwNrH4gqQ this video. And it is HILARIOUS!]]
* Duke's gleeful cackle and mimicking of complex machinery winding down broken after he trashes a turbine in "Underground" was so unexpected yet appropriate, Also, he has never felt so good about vandalism before.
* Near the end of the game:
-->'''General Graves:''' America is counting on ''you''.
-->'''Duke:''' ''[singing]'' [[Film/TeamAmericaWorldPolice America, fuck yeah!]]
* Punching out Christian Bale. Nothing more needs to be said.
** In a meta example to this, now-almost-defunct (they still barely exist as a vending machine rental service) Irish video rental chain Xtravision bundled a free DVD copy of ''Film/TerminatorSalvation'' with the game.
* In The Doctor Who Cloned Me, [[spoiler: Dylan]] becomes one of the funniest parts of series. [[spoiler: His]] best line is [[spoiler: his]] idea to get Duke [[spoiler: to the moon]] (reverse the polarity) and the follow-up. It's just how proud [[spoiler:he]] sounds about the idea that sells it.
** Voice verification.
-->'''Duke Clone:''' Repeat after me. I've got balls balls balls balls of steel.
-->'''Duke:''' I've got balls... er... balls, balls, balls of steel?
* EDF officer offers [[VideoGame/Halo2 power armor]] to Duke:
-->'''Duke:''' Power armor is for pussies.
-->'''EDF:''' Ummmm, ok... you want a gun instead?
** There are two other helmet easter eggs you can find later in the game- [[VideoGame/DeadSpace Issac Clarke's]] helmet("That's one dead space marine!") and a [[VideoGame/BorderLands Psycho]] helmet("At least he got an ending")
* The [[https://www.youtube.com/watch?v=GGrmf_NCOaQ phone messages]]
* in the DLC Captain Dylan gets thrown out of a trailer in "The Burning Bush" by a woman claiming that his "junk" looks diseased, Dylan then awkwardly tries to cover it up to Duke.
* An EDF team member gets sent to escort Duke, only to almost immediately get killed when he goes charging into the open and gets cuts down by gunfire from an alien ship
-->'''Duke:''' Dammit [[LeeroyJenkins Leeroy]]!
* In the DLC Duke gets shrunk down and has to drove a pink toy car (a TakeThat to Barbie) that has several vapid lines about how shallow girls are. Duke eventually gets fed up with it and tells it to shut up.
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