In 1984, Janssen moved to the United States to begin her professional career as a fashion model. She signed with
Elite Model Management and worked for
Yves Saint Laurent,
Giorgio Armani,
Chanel, and
Victoria's Secret. She starred in a 1988 commercial for the perfume Exclamation by
Coty. Her looks have been compared to 1940s movie stars like
Hedy Lamarr. but turned it down to pursue film roles. Her first film role was alongside
Jeff Goldblum in the 1992 crime drama film
Fathers & Sons. In 1995, Janssen appeared in
Pierce Brosnan's debut
James Bond film,
GoldenEye, as
femme fatale Xenia Onatopp. She appeared in
Lord of Illusions with
Scott Bakula. In an attempt to fight against
typecasting after her
Bond girl performance, Janssen began seeking out more intriguing supporting roles, appearing in
John Irvin's
City of Industry,
Woody Allen's
Celebrity,
Robert Altman's
The Gingerbread Man, and
Ted Demme's
Monument Ave. Denis Leary, her co-star in
Monument Ave., was impressed by how easily she blended in, initially not recognizing her, as she was already in character. She returned as Jean in the 2013 film
The Wolverine as a hallucination of Wolverine, followed by a brief cameo for
X-Men: Days of Future Past (2014). In 2002, Janssen landed the role of villainess Serleena in
Men in Black II, but had to abandon the film due to a death in her family and was replaced by
Lara Flynn Boyle. Janssen had a prominent role in the second season of the TV series
Nip/Tuck, as the seductive and manipulative
life coach Ava Moore, which earned her
Hollywood Lifes Breakthrough Artist of the Year Award. She reprised her role in the final two episodes of the series. In 2007, she starred in
Turn the River, for which she was awarded the Special Recognition Best Actress Award at the
Hamptons International Film Festival. The following year, she starred in
Luc Besson's
Taken. Janssen continued to work in television, appearing in TV pilots for
NBC's police drama
Winters and
Showtime's
The Farm, a spinoff of
The L Word, set in a women's prison. Both pilots were rejected by their networks. Janssen provided the
Dutch language narration for the Studio Tram Tour at all
Disney theme parks. She reprised her role as Lenore Mills in
Taken 2 (2012) and
Taken 3 (2014). She starred as the main villain Muriel in
Hansel & Gretel: Witch Hunters (2013). Janssen starred in the Netflix original horror thriller television series
Hemlock Grove, wherein she plays the role of family matriarch Olivia Godfrey. Janssen had a recurring role in the
ABC crime thriller television series
How To Get Away With Murder, appearing in ten episodes throughout the series, beginning her role in season two of the show and concluding it in the series finale. Janssen was cast in a starring role in the NBC crime thriller
The Blacklist: Redemption, a spin-off of the NBC series
The Blacklist, in March 2016; it was picked up to series in May 2016. The following month, Janssen expressed frustration at not being cast in
X-Men: Apocalypse, saying Hollywood was sexist toward older women. She said: "Women, it's interesting because they're replaced, and the older versions are never to be seen again... whereas the men are allowed to be both ages." In 2019, she served as a juror for the
Tribeca Film Festival. Also in 2019, Janssen joined
Jeffrey Dean Morgan in
The Postcard Killings, which was released in 2020. In 2021, Janssen starred in the Christian romantic drama film
Redeeming Love and the action-thriller
Dangerous. In a March 2021 interview, she revealed to
Forbes some details about her involvement with the
live-action adaptation of
Saint Seiya, a popular anime and manga. Janssen said that filming was supposed to take place in Europe the previous year, but production had been postponed twice due to the
coronavirus pandemic. She also hinted that she would play one of the main characters, but did not specify their name. The movie, titled
Knights of the Zodiac, was eventually released in 2023, with Janssen playing the role of Vander Guraad. In January 2026,
X-Men writer
Chris Claremont confirmed that Janssen would reprise the role of Jean Grey in
Avengers: Doomsday. ==Activism==