In a bit of a switch, Grier played the victimizer in "Women in Cages" (1972), a sadistic lesbian prison guard who tortures her charges. Her biggest hits of the 1970s, "Coffy" (1973) and "Foxy Brown" (1974), cast her as a sexy nurse who goes after the junkies who turned her sister into an addict, and the drug ring that killed her lover.

She got into big budget productions with "Fort Apache: The Bronx" (1981), as a drug-crazed cop-killer, and "Above the Law" (1988), as Steven Seagal's detective partner. Grier played a cyber substitute teacher in the sci-fi action flick "Class of 1999" (1990) and a rock club hostess in "Bill and Ted's Bogus Journey" (1991) who is later transformed into George Carlin. In 1996, Grier reteamed with several Blaxploitation stars (including Jim Brown, Fred Williamson and Richard Roundtree) for "Original Gangstas", a drama about a group of middle-aged residents of Gary, IN, who face off against current members of a gang they founded twenty years earlier. That same year, Grier also appeared in "John Carpenter's Escape from L.A." (as a transexual) and as Jim Brown's wife in "Mars Attacks!".

The actress next landed her first leading role in over 20 years when Quentin Tarantino tailored his adaptation of Elmore Leonard's novel "Rum Punch" for her. The result was "Jackie Brown" (1997), with Grier as a flight attendent who becomes enmeshed in a scam to outwit Federal agents and a gang of crooks. In 2001, Grier was cast in "Bones" a horror feature starring Snoop Doggy Dogg and most recently in Eddie Murphy's 2002 comedy, "The Adventures of Pluto Nash" (2002). She was next seen alongside Adrien Brody in the independent drama, "Love the Hard Way" (2003).