A film adaptation was made in 1968, starring Alan Arkin, Sondra Locke and Cicely Tyson.
A stage adaptation of The Heart Is a Lonely Hunter premiered on March 30, 2005, at the Alliance Theatre in Atlanta, Georgia. The show ran until April 24 of that year, then toured. The play was an Alliance Theater presentation done in association with The Acting Company out of New York. The play, adapted by Rebecca Gilman, was directed by Doug Hughes.
British artist Joe Simpson referenced McCullers' book in his 2014 painting of the same title, The Heart Is A Lonely Hunter. The painting shows two characters both reading the book on the London Underground; it is taken from his ongoing series "London".