* A great majority of the phrases The Postal Dude says based on the actions the player takes are pretty hilarious. For instance, if the player just goes around murdering innocent people, he will say phrases in order to justify himself against it:
--> [[LeaningOnTheFourthWall "I know what you're thinking, but the funny thing is I don't even like video games."]]
** If the player saves multiple times in one sitting, the Postal Dude will mock you for it.
--> "Are you saving again?!"
--> "Didn't you just save?"
** If you open the cheat option, The Postal Dude will call you a sissy. Clicking on a cheat also gives you the treat of hearing The Postal Dude say a random phrase:
-->[[NonSequitur "Butt sauce!""]]
** The amount of variants The Postal Dude exclaims [[ClusterFBomb "Fuck!"]] is amazing.
** Even the more disturbing of phrases he says are too ridiculous not to chuckle at:
--> "I suppose it would be more [[PoliticalCorrectnessGoneMad politically correct]] to kill the women and the minorities first."
--> [[HatesEveryoneEqually "I'm an equal opportunity lunatic."]]
--> [[GunNut "My president is]] [[Creator/CharltonHeston Chuck Heston]]."
--> [[OmnicidalManiac "The gene pool is stagnant, and I am the minister of chlorine."]]
* The encounter with the Vend-A-Cure 9000 after The Postal Dude gets gonorrhea:
-->[[AC:I am the Vend-A-Cure 9000. Please step forward and urinate.\\
If you have a small dick, step up closer to the plate.]]\\
''The Dude just stares at the machine''\\
[[AC:Try not to splash me.]]\\
''Dude proceeds to urinate''\\
[[AC:Damnit I said don't splash me, impotent human. Good God that is disgusting. Thanks for the urine.]]\\
''mechanical noises from within, before the machine dispenses [[MagicAntidote anti-gonorrhea pills]]''\\
[[AC:Have a nice day.]]
* [[KickTheDog Using a cat]] [[BlackComedy as a silencer for your shotgun or Machine Gun]].
* The entire encounter with Gary Coleman. When waiting in line for his autograph, the things the people say to him are hysterical. One guy greets Gary about them both going to the same rehab together, while another will scold Gary for a time they went to bar and all Gary did was hit on women. Gary will simply [[NiceCharacterMeanActor shrug each person off]] and move the line along. It's especially funny what The Postal Dude says to Gary once they meet:
--> '''The Postal Dude:''' Hey, Mr. Coleman. I love ''[[Series/TheFactsOfLife Facts of Life]]''! You ever "do" that [[Series/HappyDays Leather Tuscadero chick]]? [[note]] The joke being that Gary Coleman was in neither of these shows [[/note]]
--> ''*after signing book*''
--> '''Gary Coleman:''' [[DeadpanSnarker Thanks. You can leave now.]]
** It's made funnier when Gary threatens you with violence if he ever catches you selling it on EBay. If Gary ends up dying during the police brawl afterwards, The Postal Dude's wife will attempt to do this very thing once he returns home, since celebrity merchandise because more sought for after their death.
* The petition signing mission is pretty funny, and a good change of pace from the run-and-gun nature of the rest of the game. All you need to do is walk up to multiple random people and ask them to sign the petition. However, not everyone will immediately sign it. If you ask once, it's a friendly ask. The second attempt is The Postal Dude irritatingly asking again, wanting to be done with the whole thing in general. The third time has The Postal Dude ''threating the person with violence to themselves and loved ones if they do not sign the petition''. Most cases, [[CaptainObvious the person runs in terror at the third attempt]]... or [[InvertedTrope kindly signs the petition.]]
** Oh, and the reason for the petition? [[TakeThat To make whiney congressmen play violent video games.]]
* Just before the elephant-killing errand in ''Apocalypse Weekend'', one of the animal rights activists shows up out of nowhere and declares you must be stopped. And then one of the rampaging elephants kills him.
* After The Postal Dude raids the terrorist camp, he is arrested by National Guard. Before he is arrested, he pleads to the guards: [[BreakingTheFourthWall "Hey, it's not my fault. Book the kid with the keyboard."]]
* In ''Apocalypse Weekend'', after the elephant hunting mission, you are tasked to partake in a pigeon hunting mission. However, before you can do anything, the game is interrupted with a message claiming that Running With Scissors doesn't have the budget to include the pigeon hunting mission. [[https://www.youtube.com/watch?v=v-Mqdm6X5Po Then the game cuts to this]].
* Every single time an NPC farts, they go "Ohhh, yeah".