She also starred opposite Lucille Ball in the television drama film Stone Pillow (1985), and in the science-fiction horror sequel The Fly II (1989).

Zuniga gained major exposure for her role as Jo Reynolds on the Fox primetime soap opera Melrose Place from (1992–1996).

Other television credits include roles as Victoria Davis on One Tree Hill (2008–2012), and as Lynn Kerr on the drama series Beautiful People.

Her mother is a Unitarian minister, of Polish and Finnish descent,[citation needed] and her father, originally from Guatemala,[5] was an emeritus professor of philosophy at California State University, East Bay.

After her parents divorced, Zuniga moved with her mother and sister from Berkeley, California, to Reading, Vermont, where she spent the remainder of her teen years.

In 1987, Zuniga was cast as Princess Vespa in Mel Brooks's comedy Spaceballs, opposite Rick Moranis, Bill Pullman, and John Candy.

[17] The next year, Zuniga appeared in a lead role in the blockbuster horror film The Fly II (1988), followed by the drama-comedy Staying Together (1989), and as a med student opposite Matthew Modine in the drama Gross Anatomy (1989).

In 1992, she was cast as Jo Reynolds in the Fox soap opera Melrose Place, and appeared on the show as a regular character until 1996.

Later, Zuniga would work as a voice actor on the animated television series Stories from My Childhood (1998), and also had a lead role in the miniseries Pandora's Clock (1996), an action thriller filmed in Seattle, Washington.

[23] In 2007, Zuniga co-produced and co-directed (with Steven Latham) the documentary "The Future We Will Create: Inside the World of TED" — a look at the annual Technology, Entertainment and Design conference held in Monterey, California.

[29] In 2019, she co-starred in the television film Gates Of Paradise, opposite Lizzie Boys and Jason Priestley, and Christmas In Paris with Karl E. Ländler.

Zuniga has cited her family's camping trips to Yosemite National Park and Yellowstone as sparking her lifelong interest in the environment.

[31][32] Zuniga was a founding member of the Earth Communications Office (ECO), and has worked with the Natural Resources Defense Council, the Waterkeeper Alliance, and Environment California.

She said she had eaten sushi four times in the week prior to being taken to the emergency room and that her symptoms included weak memory, headaches, crying spells, skin rashes, and mild depression.