"Imitation of Life" was the first single released from R.E.M.'s twelfth studio album Reveal in 2001. The song struggled in the United States where the band's popularity had waned, peaking at #83 on the Billboard Hot 100 (though the song did reach #22 on the U.S. Modern Rock list, also published by Billboard). It was the lowest chart of a lead single from an R.E.M. album in the U.S. since "Fall on Me" from Lifes Rich Pageant in 1986, and no song from R.E.M. has charted in the U.S. since. However, it reached #6 on the UK Singles Charts, making it what was then the eighth top 10 for the band in Britain. In Japan, the song was extremely well received, becoming R.E.M.'s first number one single in the country.

According to the liner notes on In Time: The Best of R.E.M. 1988-2003, this song was inspired by Douglas Sirk's 1959 film of the same name.

The single's video, depicting a scene of an elaborate pool party, was shot in Los Angeles by Garth Jennings. Michael Stipe, in an interview with MTV UK in 2001, explained how the video was made. "The entire video took twenty seconds to shoot. What you're watching is a loop that goes forwards for twenty seconds, backwards for twenty seconds, forwards for twenty seconds, backwards for twenty seconds, with one camera, static, and then using a technique called 'pan and scan', which is a technical thing that is used when they go from a widescreen format and reformat to fit your television or DVD, moving in on certain parts of the entire picture. And you'll see that we do that picking up various people within the frame."

The song was placed on R.E.M.'s Warner Bros. Records "best of" album In Time: The Best of R.E.M. 1988-2003 in 2003. In the liner notes, Peter Buck states that after the release of the song he realized that the song follows roughly the same chord progression as Driver 8 from 1985's Fables of the Reconstruction.

For R.E.M.'s 2003 tour in support of In Time, the band developed a new bridge for live performances of the song. Prior to that point, the bridge consisted of full instrumentation, with Stipe's "No-one can see you cry" vocal bringing them into the chorus. The new bridge included the same lyric but echoed between Stipe and Scott McCaughey three times throughout the twenty-second midsection.

When the song is performed live, Stipe commonly alters the way in which he sings the first two choruses, using a lower register. Singing at a higher pitch, he states, is difficult to do live; on R.E.M. Live, he mentions how he "routinely sings off-key in the chorus."