What's Up with That may refer to:
Film and TV "What Up with That?", a Saturday Night Live sketch featuring Kenan Thompson begun in 2009 "What's up with that?" punchline of the April Fool in the Nickelodeon animated series The Fairly OddParents
Internet Watts Up With That?, a climate change denial blog created by blogger Anthony Watts
Music "What Up With That", song in the Saturday Night Live sketch of the same name "What's Up with That" (ZZ Top song), 1996 single composed by Billy Gibbons and Joe Hardy "What's Up with That", single by Scotty Emerick, featured in the soundtrack to the film Broken Bridges 2006 "What's Up with That", music video by Veronica Ballestrini 2007 "What's Up With That", song by Master P (featuring Silk) from Get Away Clean 1991 "What's Up With That", song by Curtis Salgado from Clean Getaway 2008 "What's Up With That", song by The Dictators "What's Up With That", song by Pee Wee Ellis composed by Alfred Ellis "What's Up With That Girl?", single by Shocking Pinks "What's Up with That Woman", song by Buddy Guy from Rhythm & Blues