The song is far better known for its cover version by Dionne Warwick and Friends. A one-off collaboration featuring Gladys Knight, Elton John and Stevie Wonder released as a charity single in the United Kingdom and the United States in 1985, it was recorded as a benefit for American Foundation for AIDS Research, and raised over three million dollars for that cause. The tune peaked at #1 for four weeks on the Billboard Hot 100 in January 1986 and became Billboard's number one single of 1986. In 1988, the Washington Post wrote, "So working against AIDS, especially after years of raising money for work on many blood-related diseases such as sickle-cell anemia, seemed the right thing to do. 'You have to be granite not to want to help people with AIDS, because the devastation that it causes is so painful to see. I was so hurt to see my friend die with such agony,' Warwick remembers. 'I am tired of hurting and it does hurt.'"
The Dionne and Friends version of the song won the performers the Grammy Award for Best Pop Performance by a Duo or Group with Vocal, as well as Song of the Year for its writers, Bacharach and Bayer Sager. It also was ranked by Billboard magazine as the most popular song of 1986.
On March 17, 1990 an AIDS benefit titled That's What Friends Are For: Arista Records 15th Anniversary Concert was held at Radio City Music Hall in New York City. One month later, CBS aired a two-hour version of the concert on television. The celebrity guests and Arista label performers were: Air Supply, Lauren Bacall, Burt Bacharach, Eric Carmen, Chevy Chase, Jane Curtin, Clive Davis, Taylor Dayne, Michael Douglas, Expose, Whoopi Goldberg, Melanie Griffith, Hall & Oates, Jennifer Holliday, Whitney Houston, Alan Jackson, Kenny G, Melissa Manchester, Barry Manilow, Milli Vanilli, Jeffrey Osborne, Carly Simon, Patti Smith, Lisa Stansfield, The Four Tops, and Dionne Warwick. "That's What Friends Are For" was the finale song sung by Warwick and cousin Houston before being joined on the stage by the other guests of the event. Over $2.5 million was raised that night for the Arista Foundation which gave the proceeds to various AIDS organizations.
Other recordings are Shirley Bassey (1991), Helen Reddy (for The Burt Bacharach Album: Broadway Sings the Best of Burt Bacharach in 1998), and the Snowcone Baritones, a barbershop quartet group at Rye Country Day School.
In the UK on the 16th December 2006, the major television network ITV aired the final of that year's series of The X-Factor, where all hopeful contestants who made it to the aired episodes performed this song live to an audience of several million.
There was a rendition of That's What Friends Are For Performed By Bill Thompson & Friends in 2006 (consisting of Bill Thompson, Allie Noble,& The Little Einsteins).
In the animated Dreamworks film Shrek the Third, the background music of this song is heard during a heartfelt conversation between two main characters.