In 1933, the novel was very loosely adapted as a movie, Advice to the Lovelorn, starring Lee Tracy, produced by 20th Century Pictures—before its merger with Fox Film Corporation—and released by United Artists. Greatly changed from the novel, it became a comedy/drama about a hard-boiled reporter who becomes popular when he adopts a female pseudonym and dispenses fatuous advice. He agrees (for a hefty payment) to use the column to recommend a line of medicines, but finds out they are actually harmful drugs when his mother dies. He then agrees to help the police track down the criminals. The movie ends with the main character happily married.
In 1957, the novel was adapted into a stage play entitled Miss Lonelyhearts by Howard Teichmann. It opened on Broadway at the Music Box Theatre on October 3, 1957 in a production directed by Alan Schneider and designed by Jo Mielziner and Patricia Zipprodt. It starred Pat O'Brien. It ran for only twelve performances.
- Main article, see Lonelyhearts
In 1958 the plot was again filmed as Lonelyhearts, starring Montgomery Clift, Robert Ryan, and Myrna Loy, produced by Dore Schary and released by United Artists. Although following the plot of the book more closely than Advice to the Lovelorn, many changes were made. The movie greatly softens the cynical edge of the original book, and the story is once more given a happy ending—the woman's husband is talked out of shooting Miss Lonelyhearts, who finds happiness with his true love, and Shrike is considerably kinder at film's end.
The film was adapted by Robert E. Bailey and Michael Dinner into a 1983 TV movie, Miss Lonelyhearts, starring Eric Roberts in the lead role. Eric Roberts would coincidentally play the lead role in the unrelated 1991 film Lonely Hearts.
In 2006, composer Lowell Liebermann completed Miss Lonelyhearts, a two-act opera. The libretto was written by J. D. McClatchy. The opera, which received its premiere April 26, 28, and 30, 2006 at the Juilliard Opera Center, was commissioned by the Juilliard School for its centennial celebration. The opera was co-commissioned by two other schools: USC's Thornton School of Music as well as the University of Cincinnati College-Conservatory of Music.
The opera was co-produced by the Thornton School of Music Opera Program at University of Southern California, and received its West Coast premiere at the school on April 20–22, 2007. Both premieres were directed by renowned stage director and Thornton faculty member Ken Cazan. Liebermann and McClatchy cleaned up a few bits of the score for this performance, having seen what needed work the preceding year.