"Come Fly with Me" was written for Frank Sinatra, and was the title track of his 1958 album of the same name. The song sets the tone for the rest of the album, describing adventures in exotic locales, in Bombay, Peru and Acapulco Bay respectively.

It subsequently became part of Sinatra's concert repertoire, and would feature in numerous performances.

The song is featured prominently in the 1963 feature film Come Fly with Me sung by Frankie Avalon. The song also appears in numerous films, including Raging Bull (1980), Dear Mr. Wonderful (1982), Betsy's Wedding (1990), Air America (1990), Vegas Vacation (1997), Little Voice (1998), Heartbreakers (2001), Catch Me If You Can (2002), and Two Weeks Notice 2001, Looney Tunes: Back in Action (2003), and PanAm (2011), and in two television bio-pics about Sinatra; the 1992 mini-series Sinatra and 1997's The Rat Pack.

The song is also used in the Cremona episode of Cabin Pressure (radio series), sung by Benedict Cumberbatch and in the episode His Way of Star Trek: Deep Space Nine, sung by James Darren. Michael Bublé also did a cover version used in the film Looney Tunes: Back in Action