Originally composed as an instrumental following the traditional 32-bar format and first recorded for Garner's 1955 album Contrasts, the tune was later paired with lyrics by Johnny Burke and became the signature song of Johnny Mathis, appearing on his 1959 album Heavenly and reaching #12 on the U.S. Pop Singles chart later that year.
It has been covered many times, by such artists as Ella Fitzgerald (1959), Sarah Vaughan (1959), Billy Eckstine (1960), Andy Williams, Frank Sinatra, The Students, Earl Grant (1961), Della Reese (1962), (Lloyd Price (1963), Richard "Groove" Holmes (1965), Donny Hathaway (1970) as a gospel song, Johnny Hartman (1971) and also by Ray Stevens (1975) as a country song. Lesley Gore included a version of the song on her 1963 debut album, I'll Cry If I Want To. Joni James recorded a version of "Misty" accompanied by acoustic guitar on her 1963 album, Like 3 O'Clock in the Morning. A version was also recorded by Julie London and an instrumental version by The Shadows. Stan Kenton recorded a version of the song on the Grammy Award winning 1962 LP Adventures In Jazz.
- Erroll Garner's version of the song was inducted into the Grammy Hall of Fame in 1991, and Johnny Mathis's version of the song was inducted in 2002. The 1975 country version by Ray Stevens won a Grammy in the category of Music Arrangement of the Year.
- Episode 309 of The Muppet Show features a mini concert by Liberace who plays the song.
- The song plays a key role in the plot of the movie Play Misty for Me (1971). Clint Eastwood and Universal paid $25,000 to use the song in the film.
- A 1976 episode of Saturday Night Live features a short film by Gary Weis (also titled Play Misty for Me), which intercuts between different performances of the song by various lounge musicians and singers.
- In an infamous scene from the twentieth episode of the fifth season  of Magnum, P.I., Tom Selleck, as Magnum, is forced to sing the first few lines of the song (before being mercifully interrupted by gunfire) in a karaoke bar, in what has become notorious as one of the worst renditions of the song ever committed to film.
- The 1986 Cheers episode "Cliffie's Big Score" has a scene where Cliff Clavin (John Ratzenberger) sings the song while attempting to seduce Diane Chambers in his car.
- Little Willie Littlefield recorded a version for his 1990 album Singalong with Little Willie Littlefield.
- In 1993, guitarist Larry Coryell covered the song for his album Fallen Angel.
- In 1993 alto saxophonist Dave Koz covered the song for his album Lucky Man.
- Clay Aiken recorded the song for his 2010 album Tried and True.
- The Johnny Mathis version of the song plays prominently in a ballroom dancing scene in the 2012 film Silver Linings Playbook.
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Mathis had heard Garner play the song, and told Garner that he'd love to sing it if Garner had lyrics for it. Garner was in attendance when Mathis later recorded the song.
Although there were already several released versions, the Mathis version recorded in 1958 popularized this virtually unknown song composed by Erroll Garner, a jazz pianist/composer, which inspired Clint Eastwood to use it in his movie Play Misty for Me, a low-budget film that proved to be a huge box-office smash. Eastwood, a fan of Mathis, ended up paying a nominal fee for the Erroll Garner recording in his film. The Mathis recording of "Misty" sold well over two million copies in the USA alone. The song is most associated with Mathis despite various recordings by artists such as Frank Sinatra, Ella Fitzgerald, and Sarah Vaughan.
In 1975, Ray Stevens released an up-tempo country rendition of this song. Stevens recounted that it was recorded on the second take when experimenting in the studio, and won a Grammy for arrangement.
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Johnny Mathis -USA-GOLD single award 1960. (over 2.5 million USA sales)