Born in New Jersey and raised in Illinois and California by her teacher parents, Manheim moved to NYC after college to pursue graduate studies at NYU. Overlooked for parts because of her size, she lost 87 pounds and became a leading player, although once she graduated and was unable to find steady employment, she gained back the weight. Fellow NYU student Tony Kushner provided a role for her Off-Off-Broadway debut in "Hydriotaphia" in 1987. Playwright-director Michael Mayer cast her in seven productions and Stephen Sondheim helped her find an agent. Manheim received an OBIE Award for her performance in a 1994 production of Craig Lucas' "Missing Persons".
While she has been able to carve a career as an actress, Manheim has often been rejected for roles because of her height and/or weight. Adamantly avoiding caricature roles, she has found work on New York-based soap operas, made four guest appearances on NBC's "Law & Order" and appeared in episodes of "Touched By an Angel" and "Chicago Hope" and had supporting roles in such projects as "Notes For My Daughter", a 1995 "ABC Afterschool Special", and the CBS TV-movie "Deadly Whispers" (1995). Manheim took home a 1998 Emmy and a 1999 Golden Globe for her work as "The Practice" hard-driving and occasionally ethically-challenged Eleanor Frutt, and her excellent dramatic work and off-screen popularity helped her survive the infamous 2003 bloodletting in which several long-standing castmembers--including leads Lara Flynn Boyle and Dylan McDermott--were released from the series. Building on her series success, Manheim nabbed supporting roles in numerous film and TV projects, including playing a post-modern Snow White in the miniseries "The 10th Kingdom" (2000), the Garry Shandling comedy "What Planet Are You From?" (2000), the respected indie "The Tic Code" (2000), the acclaimed HBO biopic "The Larramie Project" (2002), the horror movie spoof "Scary Movie 3" (2003) and director Phillip Kaufman's thriller "Twisted" (2004). In 2005 she landed the key role of Gladys Presley, mother of the future king of rock and roll in the CBS TV miniseries "Elvis," and she had a supporting turn as a school teacher in the horror thriller "Dark Water," starring Jennifer Connelly.