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"Handle with Care" is een nummer van de Brits-Amerikaanse supergroep Traveling Wilburys. Het verscheen op hun album Traveling Wilburys Vol. 1 uit 1988. Op 17 oktober dat jaar werd het nummer uitgebracht als de eerste single van het album.

"Handle with Care" is a song by the British-American supergroup the Traveling Wilburys. It was released in October 1988 as their debut single and as the opening track of their album Traveling Wilburys Vol. 1. The song was the first recording made by the group, although it was originally intended as a bonus track on a European single by George Harrison. When he and Jeff Lynne presented the song to Harrison's record company, the executives insisted it was too good for that purpose, a decision that resulted in the formation of the Wilburys. The song was written primarily by Harrison, although, as with all the tracks on Vol. 1, the writing credit lists all five members of the band: Harrison, Lynne, Bob Dylan, Roy Orbison and Tom Petty.

"Handle with Care" was the Wilburys' most successful single. It peaked at number 39 on the Cashbox Top 100 and 45 on the Billboard Hot 100 in the United States, number 2 on the Billboard Album Rock Tracks chart and number 21 on the UK Singles Chart, and was a top-five hit in Australia and New Zealand. Directed by David Leland, the video for the song was an MTV favourite in the late 1980s.

Petty and his band the Heartbreakers often performed "Handle with Care" in concert. Lynne sang it with them at the Concert for George, a year after Harrison's death in November 2001. Harrison's son Dhani Harrison sang lead on the song with Jeff Lynne's ELO during their 2019 US tour.