Milla’s last starring role came in Spike Lee’s He Got Game with Denzel Washington. She will star in Luc Besson’s upcoming Joan of Arc (slated to be released this November). In June 1999, she began performing on stage again, and there are rumors of an upcoming follow-up album to “The Peopletree Sessions”, Milla’s second album. Milla turns 24 this December.

In 1988, she had her first professional acting role in the television film The Night Train to Kathmandu, and later that year she appeared in her first feature film, Two Moon Junction. Following more small television appearances like the "Fair Exchange" (1989) and a 1989 role as a French girl (she was 14 at the time then) on a Married with Children episode and film roles, she gained notoriety with the romance film Return to the Blue Lagoon (1991). She appeared in 1993's Dazed and Confused alongside Ben Affleck and Matthew McConaughey. Jovovich then acted alongside Bruce Willis in the science fiction film The Fifth Element (1997), and later played the title role in The Messenger: The Story of Joan of Arc (1999). In 2002, she starred in the video game adaptation Resident Evil, which spawned three sequels: Resident Evil: Apocalypse (2004), Resident Evil: Extinction (2007) and Resident Evil: Afterlife (2010).

In addition to her modeling and acting career, Jovovich released a critically acclaimed musical album, The Divine Comedy in 1994. She continues to release demos for other songs on her official website and contributes to film soundtracks as well; Jovovich has yet to release another album. In 2003, she and model Carmen Hawk created the clothing line Jovovich-Hawk, which ceased operations in early 2008. In its third season prior to its demise, the pieces could be found at Fred Segal in Los Angeles, Harvey Nichols, and over 50 stores around the world. Jovovich also has her own production company, Creature Entertainment.

Jovovich is set to play Lucetta, the wife of a jailed arsonist (played by Edward Norton) in Stone, a psychological thriller starring Robert De Niro. Filming began in May 2009 at the recently closed Southern Michigan Correctional Facility in Jackson, Michigan.

Jovovich played the part of Dr. Abigail Tyler in the sci-fi thriller The Fourth Kind and will star in the psychological thriller Faces in the Crowd, which is written and directed by Julien Magnat; in the latter film, she plays the survivor of a serial killer’s attack that leaves her suffering from a condition called prosopagnosia, which renders her unable to recognize faces.

Jovovich will return for her role as Alice, in the fourth movie of the Resident Evil series Afterlife, which is directed by her husband Paul W. S. Anderson. She is set to star in David R. Ellis horror flick Bad Luck which based on a screenplay by David Schouw.