Up in Smoke is a 1978 film featuring Cheech and Chong.

Up in Smoke may also refer to:

• Up in Smoke (album), the soundtrack to the 1978 film
  • "Up in Smoke", title track from the 1978 album and the film's theme song, originally recorded by Cheech and Chong, later covered by Hank Williams III on his 2006 album Straight to Hell
• Up in Smoke (album), a 1995 album by Indo G and Lil' Blunt
• Up in Smoke (1957 film), starring the comedy team of The Bowery Boys
• Up in Smoke (2015 film), starring Naathan Phan
• "Up in Smoke" (CSI: Crime Scene Investigation), a sixth-season episode of CSI: Crime Scene Investigation
• "Up in Smoke" (NCIS), a ninth-season episode of NCIS
• Up in Smoke Tour, a West Coast hip hop tour which took place in 2000
• Up in Smoke, an alternate name used by the professional wrestling tag team Cheech and Cloudy
• "Up in Smoke", a song by Hollywood Undead from Notes from the Underground
• "Up in Smoke", a song by Lower Than Atlantis from World Record
• "Up in Smoke", a song by Neck Deep from A History of Bad Decisions