Trivia

Camel withdrew a $5,000 sponsorship because of the scene in which Dez tells Roberta that she "should stop smoking."

Major scenes take place in two famous landmarks of the New York "Downtown" art scene: Gary Glass tracks down Susan at Danceteria, the New Wave nightclub where Madonna first performed; also, Dez works at the Bleecker Street Cinema, one of the most famous "art house" theaters in New York City.

It was important to Susan Seidelman to incorporate the "colorful and diverse terrain of the New York area" into the film, according to the production notes. The director created two disparate worlds for Roberta and Susan, with Roberta's suburban New Jersey surroundings cast in "soft pastel tones," and Susan's gritty Manhattan environment "in saturated primary colors" to convey mystery and magic. Production designer Santo Loquasto worked to give the portion of the film in which Roberta enters Susan's world a fantasy-like quality, as Seidelman wanted Roberta's arrival in New York City to represent "the beginning of the trip down the rabbit hole," referring to Lewis Carroll's Alice's Adventures in Wonderland (London, 1865).

Exterior shots of Manhattan showed alleyways and backstreets in SoHo and the East Village, with locations on St. Marks Place, Avenue C, and Great Jones Alley. The nightclub scenes where "Gary Glass" and Susan meet for the first time were shot at the New York nightclub Danceteria, and the set for The Magic Club was built in the Audubon Ballroom, located on 166th and Broadway. The Glass home was the result of a careful blending of two distinct locations: a house in Tenafly, New Jersey, and a condo in Bayside, Queens. According to DVD commentary by the filmmakers, multiple endings to Desperately Seeking Susan (1985) were shot.

The identical triplets dressed in matching outfits outside the publishing house where Madonna places a personal column were triplets not originally in the script. The director Susan Seidelman noticed them walking down the street while setting up the shot and wanted them in the scene, as they captured the movie's theme of doubling. These three brothers, Robert Shafran, David Kellman and Eddy Galland, were separated at birth and received a great deal of publicity when they finally meet as adults. They were later the subject of the documentary Three Identical Strangers (2018).

Upon reading the script for the first time, Rosanna Arquette expressed her desire to play the role of Susan. She was surprised to discover the producers wanted her to play the lead role of Roberta.

The producers couldn't get Kevin Costner or Dennis Quaid to read for the role of Dez. With two female leads, some actors didn't want to be third fiddle.