In 1981, Thomas began her run as cop Lucy Bates on "Hill Street Blues" (NBC, 1981-87). Over the course of the series, she went from inexperienced rookie to confident sergeant and earned seven Emmy nominations (Best Supporting Actress) for her work, taking home the award for the 1984-85 season. Thomas spent hours on the set observing the directors, becoming enamored of the profession, but executive producer Steven Bochco would not allow her to helm any "Hill Street" episodes. He became, however, her biggest advocate, hiring her to direct episodes of "Hooperman" (ABC, 1987-89), then entrusting her with the premiere episode of ABC's "Doogie Howser, M.D." in 1989. Thomas, who had recently played the over-zealous troop leader Velda opposite Shelley Long in "Troop Beverly Hills" (1989), her first feature in seven years, turned her back on acting to direct episodes of such series as "Star Trek: The Next Generation", the pilot and premiere episode of the short-lived ABC series "Arresting Behavior" and several episodes of the HBO series "Dream On", for which she won her second Emmy as Best Director. A TV-movie and another Emmy nomination followed for "My Breast" (CBS, 1994), which examined the impact of breast cancer on one woman (Meredith Baxter) and her family.

Thomas made her feature directorial debut with the direct-to-video romantic comedy "Only You" (1992), starring Andrew McCarthy and Kelly Preston. In 1995, she had her shot at another feature film. Handed a mere $12 million budget, she turned "The Brady Bunch Movie" into something both satiric and celebratory. With an unqualified hit, Thomas found she had helmed one of the highest grossing films (in excess of $60 million) directed by a woman, putting her in the same category with Penny Marshall and Penelope Spheeris. She helmed "The Late Shift" (HBO, 1996), a film based on the book about the late night talk show wars and the choosing of Johnny Carson's successor, before returning to features to direct shock jock Howard Stern in "Private Parts" (1997), both projects in collaboration with producer Ivan Reitman. Her stock, which had soared with the screen adaptation of Stern's autobiography, slipped some with the lame updated version of "Dr. Dolittle" (1998), but to Thomas' credit, there was a general seamlessness in the manner the humans, real critters and inventions interacted.The rehab comedy "28 Days" (2000) was about as dark a vehicle as Sandra Bullock could carry at that point in her career, and while it was no great shakes at the box office Thomas did a journeyman job balancing the elements of humor and seriousness the film offered without descending into after-school special territory. Her next effort, the 2002 feature film version of the hit 1960s TV comedy "I Spy," demonstrated that Thomas still retained a comedic gift, frequently capturing genuinely hilarious interplay between co-stars Eddie Murphy and Owen Wilson. The film's leaden action sequences and convoluted plot logic lacked the same creative spark, however.