Ruehl began her career in regional theatre with the Denver Center Theatre Company, taking odd jobs between engagements. In 1980, she was nearly cast in the sixth season of Saturday Night Live, losing her slot to Denny Dillon. Her first starring role on Broadway came in 1984's "I'm Not Rappaport". She then went on to win the 1984 Obie Award for her performance in "The Marriage of Bette and Boo" and twenty years later, an Obie for "Woman Before a Glass". She also received a 1991 Tony Award as Best Actress (Play) for Neil Simon's "Lost in Yonkers" and continued her role in the show during its tour with co-star Mercedes McCambridge. Her performances in two other plays earned her two other Tony nominations: in 1995, as Best Actress (Featured Role – Play) for a revival of "The Shadow Box"; and in 2002, as Best Actress (Play) for Edward Albee's "The Goat, or Who is Sylvia?".