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Once in a Lifetime is een nummer van Talking Heads dat in februari 1981 op single werd uitgebracht, en dat is terug te vinden op het album Remain in Light uit 1980.

"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 January 1981 through Sire Records as the lead single from the band's fourth studio album, Remain in Light (1980).

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 about 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 platinum in the UK in 2023. 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 named it one of the "500 Songs that Shaped Rock and Roll", and Rolling Stone placed it at number 28 on its 2021 list of "The 500 Greatest Songs of All Time".