Born in Sarasota, FL, Gugino moved to California at the age of four after her parents divorced. Raised by a free-spirited mother, Gugino had a most unconventional childhood. Frequently on the move, Gugino and her mother lived for a period of time inside a teepee and later, in a van in Big Sur. Splitting her summers in Florida with her father, Gugino adapted to her lack of stable domesticity remarkably well. A straight-A student throughout high school, Gugino even graduated as her senior class valedictorian. Gugino also had beauty to match the brains. Discovered by a modeling agent in the mid-1980s, Gugino was whisked away to New York at the age of 15. Ultimately deemed too short for the catwalk, however, the 5'4" Gugino watched her modeling career stall relatively quickly. Overwhelmed and disappointed, Gugino moved back to California that summer. It was there that at the suggestion of her aunt, actress Carol Merrill, Gugino began to take acting classes.Gugino's screen career took off almost immediately. Starting with a 1988 guest-spot on "Who's The Boss?" (ABC, 1984-1992), Gugino continued to work steadily. In 1989, she landed her first major break with a recurring role on the popular nighttime drama "Falcon Crest" (CBS, 1981-1990). More guest-starring roles would follow in subsequent years on such popular hits as "Doogie Howser, M.D." (ABC, 1989-1993), "The Wonder Years" (ABC, 1988-1993) and "Quantum Leap" (NBC, 1989-1993). In 1996, Gugino landed one of her earliest high-profile roles as sexy reporter Ashley Schaeffer, the love interest of Deputy Mayor Mike Flaherty (Michael J. Fox), in the first 12 episodes of "Spin City" (ABC, 1996-2002). Halfway through its maiden season, however, Gugino's character was written out, for reasons unclear. Gossipmongers, however, suggested that Gugino's dismissal might have been due to pressure from Fox's wife, actress Tracey Pollan, who was reportedly jealous of Gugino and Fox's onscreen chemistry.At the same time that Gugino's face was becoming familiar on TV, her film career was simultaneously maturing. In 1993, Gugino co-starred in the inane comedy "Son-in-Law," starring Pauly Shore. A supporting role in 1995's comedy "Miami Rhapsody" followed. Gugino next landed a meaty role opposite Nicolas Cage in the overblown action-thriller "Snake Eyes" (1998). None of these roles, however, met with any substantial critical notice. With the new millennium, however, Gugino began to have better luck picking her roles. In 2001, director Robert Rodriguez cast Gugino as spy mom Ingrid Cortez, Antonio Banderas' better half, in "Spy Kids," the first of the highly-profitable "Spy Kids" movie trilogy. Made on a relatively modest budget of $35 million, "Spy Kids" went on to become a $200 million international juggernaut and spawned two sequels, "Spy Kids 2: Island of Lost Dreams" (2002) and "Spy Kids 3-D: Game Over" (2003). Determined to be taken seriously as a film actress, Gugino turned down the chance to play Vin Diesel's love interest in the hit comedy "The Pacifier" (2005) in order to take a small but memorable role as Lucille, a lesbian parole officer, in Robert Rodriguez's "Sin City" (2005), a filmic adaptation of writer-artist Frank Miller's graphic novel series. An ultra-violent, neo-noir extravaganza, "Sin City" was an unholy hit, grossing nearly $160 million worldwide.In 2003, Gugino returned to television to star on the short-lived crime drama, "Karen Sisco" (ABC, 2003-04). Based on a creation by legendary crime novelist, Elmore Leonard, the title role of Karen Sisco was originally portrayed by Jennifer Lopez in another Leonard adaptation, the tightly crafted Stephen Soderbergh crime caper, "Out of Sight" (1998). Despite strong reviews, however, "Karen Sisco" was yanked after just 10 episodes. Coming back in 2005, Gugino starred on the short-lived sci-fi drama "Threshold" (CBS, 2005-06). After a promising start, "Threshold" began to stumble in the ratings. In an effort to boost sagging ratings, the series was moved from Friday nights to Tuesdays. Unfortunately, the plan backfired and the ratings continued to drop sharply. In November of 2005, CBS finally pulled the plug on "Threshold" with four episodes yet to be aired.Adding stage work to her many accomplishments, Gugino gilded her résumé in late 2006 with a starring role in the off-Broadway production of Tennessee Williams' drama, "Suddenly, Last Summer," opposite Blythe Danner. After the play wrapped, Gugino returned to L.A., where she promptly won a starring role in the Ben Stiller comedy, "Night at the Museum" (2006). The film's financial success, no doubt helped Gugino land her next gig: a juicy role on one of television's hottest comedies, "Entourage." In early 2007, the hip show's creator-producer Doug Ellin announced that Gugino would join the cast for its fourth season. As Amanda, the mysterious new über-agent of Vincent Chase (Adrian Grenier), Gugino squared off against Vincent's egomaniacal ex-agent, Ari Gold (Jeremy Piven), proving herself a sizzling foil with her sharp timing and wit.Back on the big screen, Gugino played the wife of a tough, savvy cop (Russell Crowe) who has no problem cheating on her, even though he upholds honor and integrity on the streets in "American Gangster" (2007). In "The Lookout" (2007), she delivered a brief, but memorable performance as the therapist to a former jock (Joseph Gordon-Levitt) suffering memory loss after a serious accident who is duped into helping to rob a bank. Gugino next played a crime scene investigator with romantic ties to a New York City detective (Robert De Niro) investigating a serial killer in the forgettable crime thriller "Righteous Kill" (2008). After a small supporting role in the terribly reviewed supernatural thriller "The Unborn" (2009), Gugino co-starred in the first big blockbuster of the year, "Watchmen" (2009), playing Sally Jupiter, a retired superhero and the first to be Silk Spectre. She went on to play a discredited astrophysicist opposite Dwayne "The Rock" Johnson in "Race to Witch Mountain" (2009), before landing a recurring role as Hank Moody's (David Duchovny) attorney on "Californication" (Showtime, 2007-14). After co-starring in the critically derided "Sucker Punch" (2011), she joined Jim Carrey for "Mr. Popper's Penguins" (2011) and an all-star ensemble cast for the holiday vignette "New Year's Eve" (2011). Back on television, she reprised U.S. Marshal Karen Sisco - now renamed Karen Gooddall - for a third season episode of "Justified" (FX, 2010-15). Gugino next starred on Cameron Crowe's short-lived TV effort "Roadies" (Showtime 2016) before starring in science fiction romance "The Space Between Us" (2017) and Stephen King thriller "Gerald's Game" (2017). Gugino returned to TV in the lead role of an adaptation of the Shirley Jackson classic "The Haunting of Hill House" (Netflix 2018).