Kier and German director Rainer Werner Fassbinder had previously been teenage lovers and street hustlers in the Frankfurt gay scene in the early 1960s. Beginning in the late 1970s, Kier was cast in a number of Fassbinder features. It was a period in which Kier was also living in Fassbinder's Munich household, running the kitchen. He played the hairdresser with whom the station master's wife had an ongoing affair in "Bolwieser/The Stationmasters' Wife" (1978) and was one of the terrorists in the black comedy "Die Dritte Generation/The Third Generation" (1979). Kier had small roles in the episodic masterpiece "Berlin Alexanderplatz" (1980) which was originally made for German television, as well as parts in "Lola", and "Lili Marlene" (both 1981), the latter being one of Fassbinder's takes on life in Nazi Germany.
Kier also appeared in Werner Schroeter's "Flocons d'Or" (1978) and had the title role in Walerian Borowczyk's "The Blood of Doctor Jekyll" (1981), both made in France. He starred in a number of German-produced films in the mid-1980s including the Monika Treut/Elfi Mikesch directed "Seduction: The Cruel Woman" (1985). Danish director Lars von Trier, for whom Kier has become something of a regular player, gave him leads in the experimental horror feature "Epidemic" (1987) and the stunning political thriller "Zentropa/Europa" (1991). Von Trier also gave Kier one of the most memorable entrances in the history of cinema in the bizarre comedy-thriller "The Kingdom" (1994), a film in four parts originally made for Dutch TV. (Kier reprised the role in the 1997 sequel "The Kingdom II".) Returning to the USA, Gus Van Sant cast him as a john who goes after River Phoenix in "My Own Private Idaho" (1991; hilarious with his deadpan rendition of the line "I'm so excited") and as a commercial director in "Even Cowgirls Get the Blues" (1993). Mainstream audiences may remember Kier from the blockbuster "Ace Ventura: Pet Detective" (1994), wherein he played a shady entrepreneur or from "Barb Wire", as Pamela Anderson Lee's sidekick, and Steve Barron's "The Adventures of Pinocchio" (both 1996), as the villainous puppetmaster Lorenzini. He reprised the latter three years later in "The New Adventures of Pinocchio".
From the late 90s on, Kier seemingly found a niche in horror films, many with vampires at their core. In "Blade" (1998), he was deliciously monstrous as the venal bloodsucker Dragonetti and acted in such other genre outings as "Modern Vampires/Revenant" (also 1998) and "Besat/Possessed" (1999). In a similar vein, Kier offered a fine turn as art director and producer Albin Grau in "Shadow of the Vampire" (2000), a fictionalized musing about the behind the scenes making of the 1922 F W Murnau classic "Nosferatu".