The song is sung all the way through once in the musical by Don Quixote as he stands vigil over his armor, in response to Aldonza (Dulcinea)'s question about what he means by "following the quest". It is reprised partially three more times—the last by prisoners in a dungeon as Miguel de Cervantes and his manservant mount the drawbridge-like prison staircase to face trial by the Spanish Inquisition.
It was awarded the Contemporary Classics Award from the Songwriter’s Hall of Fame.
The song is strongly associated with the 1967 Boston Red Sox, as their pennant-winning season was popularly dubbed "The Impossible Dream." 
On the television show Gomer Pyle, U.S.M.C., in an episode entitled "The Show Must Go On," which aired November 3, 1967, Jim Nabors, as Pyle, sang a version of the song. In the episode, it is alluded that Pyle's audience might possibly include "the President," who, at the time, was Lyndon Johnson.
During Robert Kennedy's long shot campaign for the presidency in 1968 George McGovern introduced him before a South Dakota stump speech by quoting from The Impossible Dream. Afterwards Kennedy questioned whether McGovern thought it was impossible, McGovern said "No I don't think it's impossible. I just...wanted the audience to understand it's worth making the effort – whether you win or lose." Kennedy replied, "well, that's what I think."  It was actually Robert Kennedy's favourite song and Andy Williams who covered the song was a close friend. The song was also a favourite of younger brother Ted Kennedy and was performed by Brian Stokes Mitchell at his memorial service in 2009.
The song is spoofed by British comedian John Cleese as part of his December 1977 appearance on The Muppet Show. For the show's closing number, as the opening chords of The Impossible Dream play in the background, Kermit the Frog introduces a rather bewildered Cleese – who immediately demands to speak with Kermit. Cleese then tells the frog that he refuses to sing old show tunes. Kermit apologizes and a few seconds later, the curtain reopens, this time with Cleese dressed as a Viking, as Sweetums attempts to duet with him in Wagnerian opera. Cleese isn't thrilled with this either,so they try putting him in a Mexican maraca solo costume. When Cleese tells Kermit that "there's no way I'll do a song", the pigs and monsters he didn't want to work with are brought out on stage.
JOHN CLEESE: You were supposed to be my host. How could you do this to me? Kermit – I am your guest!
CAST: (singing to "Impossible Dream") This is your guest – To follow that star...
An episode of the 2nd season of the television series Quantum Leap, aired December 6, 1989, is entitled "To Catch a Falling Star". In this episode, Sam "leaps" into the body of an understudy to an alcoholic actor in order to prevent him taking a fatal fall during a performance of Man of La Mancha. Sam's "host" takes over for the actor, and at the end of the episode, sings The Impossible Dream. The alcoholic actor is played by John Collum, who alternated with Richard Kiley in the original stage run of Man of La Mancha.
An episode of the 8th Season of the television series Touched by an Angel, aired May 4, 2002, is entitled "The Impossible Dream". It was written by Brian Bird, directed by Peter H. Hunt and features Luther Vandross as Reggie Hunter, a janitor in his former high school with a great voice that gave up a singing career twenty-five years early. At the end of the episode, he sings The Impossible Dream in a concert to honor his Aunt Charlotte, a choral teacher, who is retiring.