With their historic theater slated for demolition, the cast and crew of a popular, variety style radio program prepare for their last show. The folksy host, Garrison Keillor (GARRISON KEILLOR), doesn't seem fazed by their swan song, since he's always viewed their latest performance as potentially their last.
As security guard Guy Noir (KEVIN KLINE) keeps dibs on a Dangerous Woman (VIRGINIA MADSEN) who's shown up backstage, very pregnant stage manager Molly (MAYA RUDOLPH) tries to keep Keillor and his various performers on time. They include sisters Yolanda (MERYL STREEP) and Rhonda Johnson (LILY TOMLIN), the singing duo remainder of a former quartet. While Yolanda's daughter Lola (LINDSAY LOHAN) delves into suicidal poetry, her mom and aunt reminisce about the good old times.
Another old-time act consists of Dusty (WOODY HARRELSON) and Lefty (JOHN C. REILLY), two cowpokes who alternate between country ditties and bad when not risqué jokes, while old country crooner Chuck Akers (L.Q. JONES) is sweet on lunch lady Evelyn (MARYLOUISE BURKE). Despite the arrival of the corporate Axeman (TOMMY LEE JONES), the cast and crew keep the show going toward its final conclusion, all while Guy tries to figure out what the mysterious woman -- who turns out to be an angel of death -- wants with them.