"Once in a Lifetime" is a song by the American new wave band Talking Heads, produced and cowritten by Brian Eno. It was released in November 1980 as the lead single from Talking Heads' fourth studio album, Remain in Light (1980), through Sire Records.

Eno and Talking Heads developed "Once in a Lifetime" through extensive jams, inspired by Afrobeat musicians such as Fela Kuti. David Byrne's vocals were inspired by preachers delivering sermons, with lyrics addressing existential crisis and the unconscious. The music video, directed by Byrne and Toni Basil, has Byrne dancing erratically over footage of religious rituals.

"Once in a Lifetime" was certified gold in the UK in 2021. A live version, taken from the 1984 concert film Stop Making Sense, charted in 1986 on the Billboard Hot 100. NPR named "Once in a Lifetime" one of the 100 most important American musical works of the 20th century. The Rock and Roll Hall of Fame lists it as one of the "500 Songs that Shaped Rock and Roll", and Rolling Stone ranked it at number 27 on its 2021 list of "The 500 Greatest Songs of All Time". The music video has been named among the greatest by several publications.