The story follows a British journalist, Arthur Stuart (Christian Bale), who has to search his own past when writing an article about the mysterious disappearance of a former glam-rock star, Brian Slade (Jonathan Rhys Meyers), for an American periodical. The film turns Slade's paranoia of being murdered during a concert (a paranoia that Bowie incorporated into the Ziggy Stardust story in the climax of the Ziggy Stardust album) into a career-ending publicity stunt by Slade, after which he gradually disappears from the public view entirely. As Stuart locates and talks with people connected to Slade, trying to find out what happened, he revisits the glam-rock scene of the '70s in a series of vignettes, which recreate the stories of Slade, Slade's collaborator and one time lover Curt Wild (Ewan McGregor) and others involved in their lives.

The film centers on Brian Slade (Jonathan Rhys Meyers), a bisexual glam rock icon patterned after David Bowie and, to a lesser extent, Marc Bolan. Ewan McGregor co-stars in the role of Curt Wild, a genre defying performer who doesn't back down from sex, nudity, or drugs on or off stage, and whose biographical details are based on Iggy Pop (who grew up in a trailer park) and Lou Reed (whose parents sent him to electroshock therapy to 'cure' his homosexuality). Also featured are Christian Bale as a young glam rock fan and reporter, Arthur Stuart; Toni Collette as Slade's wife, Mandy; Eddie Izzard as his manager, Jerry Devine; and Luke Morgan Oliver as a young Oscar Wilde.

The tale strongly parallels Bowie relationships with Reed and Pop in the 1970s and 1980s. Brian Slade's gradually overwhelming on-stage persona of "Maxwell Demon" and his backing band, "Venus in Furs", likewise bear a resemblance to Bowie's similar persona and backing band, Ziggy Stardust and the Spiders from Mars. And like the relationship of Slade and Wild, Bowie produced records with both Iggy Pop and Lou Reed.

Haynes has said that the story is also about the love affair between America and Britain, New York and London, in the way each music scene feeds off and influences each other. Little Richard is shown as an early influence on Brian Slade. In real life Little Richard inspired the Beatles and Bowie, who in turn inspired many bands to come after. Little Richard has also been cited by Haynes as the inspiration for Jack Fairy.

As an American, Haynes sees the glam scene as an outsider, just as the character of Arthur sees the world of his idols, Slade and Wild. While the film is described as being about Bowie / Slade, the film is also about the teenage fans of glam rock and the adolescent experience of finding one's identity. The notion of self-invention, a theme in the life and works of Oscar Wilde as well as in the personae of Ziggy and Iggy, gives teenagers a natural impetus to emulate the outrageous clothes and make-up of glam rockers.

The film is strongly influenced by the ideas and life of Oscar Wilde (seen in the film as a progenitor of glam rock), and refers to events in his life and quotes his work on dozens of occasions. The work of Jean Genet (the subject of Haynes' previous film, Poison) is referred to in imagery and also quoted in dialogue.

The narrative structure of the film is modeled on that of Orson Welles' Citizen Kane, in that reporter Stuart tries to solve a mystery about Slade, traveling around to interview Slade's lovers and colleagues, whose recollections are shown in 1950s, 1960s and 1970s flashback sequences.

The film wasn't successful at the box office, making just $1.5m on a budget of $9m, according to Christine Vachon's 2006 account of independent film producing, A Killer Life. The film would later become a cult classic.[citation needed]

Although the character of Brian Slade is heavily based on David Bowie, Bowie himself disliked the script and vetoed the proposal that his songs appear in the film.

The finished soundtrack includes songs by glam rock and glam-influenced bands, past and present.