Once in a Lifetime is a play by Moss Hart and George S. Kaufman, the first of eight on which they collaborated in the 1930s.

The satirical comedy focuses on the effect talking pictures have on the entertainment industry. When the New York City vaudevillean team of Jerry Hyland, May Daniels, and George Lewis find themselves in a faltering vaudeville act, they decide to head west and present themselves as elocution experts in the hope someone will hire them to train actors unaccustomed to speaking on screen. On the train they meet gossip columnist Helen Hobart, who introduces them to megalomaniac film mogul Herman Glogauer when they arrive in Hollywood.

The trio's misadventures include encounters with Lawrence Vail, a New York City playwright driven to distraction and eventually a sanatorium by studio bureaucracy and a lack of work to keep him busy; silent screen beauties Phyllis Fontaine and Florabel Leigh, whose voices sound like nails on a blackboard; two pages in 18th-century dress who periodically arrive carrying placards with announcements about Glogauer's latest doings; a ditzy receptionist who wears an evening gown to work; and aspiring actress (and proverbial dumb blonde) Susan Walker and her chaperoning stage mother.

Dimwitted George becomes a director who shoots the wrong script, forgets to turn on the soundstage lights, and audibly cracks nuts during filming, yet his movie is called a masterpiece and he's declared a genius by trend-conscious journalists who believe he's ahead of his time.