The running gags in the show are:
- somebody laughing at Toffee's name
- somebody spelling NOS-4-A2's name wrong
- Envy being mistaken for a woman
- a character saying "Shut up, you old hag!" to an older character (either by animated or real age)
- a character breaking the 4th wall
- traditional cartoony gags: wild takes, eye popping, slapstick, et cetera
- making references to popular culture, history and real life
- Jasper, madame Gasket and dr. Girlfriend being mistaken for men
- calling Shen "mr. Scissorfeet"
- catchphrases
- a character disgusted by an other character's ugliness (like Chef, Murdoc, et cetera)
- Murdoc being called a "goblin" or other creature
- dr. Cockroach getting slapped on the head as a result of his mad laughter
- Smarty hitting Stupid on the head with his own bat after saying something stupid
- Tulip talking to herself
- Death the Kid's perfectionistic tendencies, especially his obsession with symmetry
- Greasy flirting with every woman he sees
- Wyatt getting knocked unconscious right before country music starts playing
- a group of a few random citizens talking in perfect synchronization
- Shen getting angry after being called an "albino" or getting a tail feather pulled out
- Edward getting angry after being called "short" or "small"
- various toons believing that Posey is nervous, upset or at the edge of mental breakdown, due to her voice