Leonard Foglia (Thurgood, Master Class) directs. Opening is Oct. 7 for a run scheduled through Nov. 8 in midtown.

"Channeling a dramatic range of interview subjects, from artists and athletes to doctors and those they treat," Smith, according to a Let Me Down Easy synopsis, explores "the power of the body and the resilience of the human spirit, featuring first person accounts from a wide variety of sources, including Lance Armstrong and former Texas Governor Ann Richards."

Smith, as she did in her acclaimed Twilight: Los Angeles, 1992, uses her trademark character interpretations to channel all her subjects on stage.

The work previously played in developmental versions at New Haven's Long Wharf Theatre and Boston's American Repertory Theatre in 2008.

The design team includes Riccardo Hernandez (scenic), Ann Hould-Ward (costumes) and Jules Fisher and Peggy Eisenhauer (lighting). Smith was recently seen in the first season of Showtime's "Nurse Jackie" opposite fellow stage veteran Edie Falco. The actress has also been seen on television's "The West Wing," "The Practice" and the films "Rachel Getting Married," "The American President," "Philadelphia" and "Dave." As a writer, she has penned the plays Fires in the Mirror (Pulitzer Prize finalist) and House Arrest as well as the books "Talk To Me" and "Letters to A Young Artist."

Let Me Down Easy launches the new season at Second Stage. The 2009-2010 roster will continue with John Lithgow and Jennifer Ehle in the world premiere of Douglas Carter Beane's Mr. & Mrs. Fitch (Jan. 26-March 21, 2010) and Paul Weitz's Trust (spring 2010). A fourth production is yet to be announced.

For tickets to Let Me Down Easy at Second Stage, 307 West 43rd Street (off Eighth Avenue), call (212) 246-4422 or visit 2ST.com.