Once in a Lifetime is comedic play by Moss Hart and George S. Kaufman. Similar to the more famous movie Singin' in the Rain, its plot revolves around the introduction of the "talkie" to Hollywood.

It was made into a movie in 1932, directed by Russell Mack and starring, among others, Jack Oakie, Zasu Pitts, and Alan Ladd (in an uncredited small part). The movie was remade in 1963 with George Hamilton and a book much later.

Once in a Lifetime is also a 1997 pornographic movie, starring Sunset Thomas.

Once in a Lifetime is also a song by Talking Heads, off their album Remain in Light.