Frank Sinatra first sang the song on his weekly radio show in 1946, as the second part of a medley with "Easy to Love". He put his definitive stamp on the tune ten years later, in a swinging big-band version that built to successive climaxes on the back of an arrangement by Nelson Riddle. Riddle was a fan of Maurice Ravel, and has said that this arrangement was inspired by the Boléro. Sinatra aficionados usually rank this as one of his finest collaborations with Riddle's orchestra. An insistent saxophone section propels the chart which climaxes in a startlingly out-of-control slide trombone solo by Milt Bernhart. Appreciating the excitement of the arrangement, Sinatra usually included the song in his concerts thereafter—a tradition carried on by Sinatra's son, Frank Jr.
Sinatra re-recorded "I've Got You Under My Skin" for the album Sinatra's Sinatra (1963), an album of re-recordings of his personal favorites. This time the trombone solo was by Dick Nash because Bernhart was booked for another session.
A live version of the song also appears on the 1966 album "Sinatra at the Sands" featuring Count Basie and his orchestra.
Neneh Cherry's hip-hop interpretation of the song was the lead single for the Red Hot + Blue charity album, and reached number 25 in the UK Singles Chart. The music video was directed by Jean-Baptiste Mondino.
Neneh Cherry replaced most of the lyrics with a rap on AIDS victims and how society reacts to them. Of the original Cole Porter lyrics, she kept only the first four lines and "Use your mentality, wake up to reality".
The 2009 action film Gamer includes the Sammy Davis Jr. version of the song in a musical number in which Ken Castle, the villain (played by Michael C. Hall), lip-syncs it to show he has the ability to control people with technology.