Once in a Lifetime is a three-CD box set by American post-punk/new wave band Talking Heads, released in the United States by Sire, Warner Bros, and Rhino in 2003.

The discs are packaged in a wide horizontal book that recalls a CD longbox, featuring paintings by Russian artists Vladimir Dubossarsky and Alexander Vinogradov and with art direction by Stefan Sagmeister (for which he received a 2005 Grammy Award for Best Boxed or Special Limited Edition Package).

Other non-album tracks are: "Sugar on My Tongue"—a 1975 studio demo, dating from when the band was still a trio (minus Jerry Harrison); the 1977 non-album single "Love → Building on Fire", the "Psycho Killer" B-side "I Wish You Wouldn't Say That"; and two Naked-era songs – "Sax and Violins" (finished in 1991 for the soundtrack to the film Until the End of the World) and "Lifetime Piling Up" (finished in 1992 for the Sand in the Vaseline compilation).

This box set marked the first CD release of "A Clean Break", a 1977 live recording from 1982's The Name of This Band Is Talking Heads.

Once in a Lifetime contains four previously unreleased "alternate versions", three of which would later be reissued in various forms: "Uh-Oh, Love Comes to Town" and "New Feeling" are the original Tony Bongiovi "pop experiment" mixes, including brass parts and other more "commercial" production techniques that the band ultimately rejected; "Cities" is an alternate take that includes a verse previously heard only in live performances (most notably in a deleted scene from Stop Making Sense); and "Drugs" is an early mix of the song, featuring Robert Fripp on guitar and very different production and instrumentation than the final version.