Writer-director Paul Schrader experienced a unique problem while filming was underway in New York City. The film is set during a sanitation worker strike which called for large amounts of uncollected trash to be prominently featured in exterior scenes. But since the real New York City sanitation department was very much on the job they would inadvertently collect trash that was meant to be a part of the film's production design.
In one scene, John LeTour (Willem Dafoe) is shown sitting on his bed watching old photographs and listening to some CDs. One of the CDs is the soundtrack from Walter Hill's Streets of Fire (1984), which was Dafoe's first starring role.
Director Paul Schrader actually sent Willem Dafoe out to observe deals with a real drug dealer as training for this role. When Schrader asked Dafoe if anybody recognized him, Dafoe said he believed some did, but that they were afraid they would not get their drugs if they said anything.
When questioned about what the film's title meant, Willem Dafoe joked that the other two films in Schrader's trilogy of loners were titled after the key characters occupations. He jokingly said Schrader thought no one would watch a film if it was just called "Drug Dealer".