The story of The Misfits (1961) was conceived when playwright Arthur Miller waited out his own divorce in Nevada and was impressed by the way the region's isolation and alienation affect and reflect its residents. He also saw a means of providing a suitable but challenging screen role for the woman he was planning to marry, Marilyn Monroe. The project drew director John Huston plus actors Clark Gable, Montgomery Clift, Eli Wallach, and Kevin McCarthy, who arrived in Reno to what the San Francisco Chronicle reported as "gape jawed movie fans stacked twelve deep along the sidewalks in front of Harrah's Club in Reno."

The project was shot in sequence on existing locations including Harrah's in Reno and the former Mia's in Dayton. The stunning finale used a dry lakebed off Highway 50 near Stagecoach, now known as Misfits Flat. The sequence shows director John Huston's trademark skill with rugged location work, contributing to the film's eventual ranking as a classic. Horses running wild on an expanse of flat desert emphasize all the characters' fear of being reigned in as the Old West loses ground, though instead of herding horses for ranch and rodeo use, the cowboys sell them to the meat industry. The wild mustang, a classic symbol of the free West, has become dog food. Catching horses, says Gay, is "like ropin' a dream now."

Though the movie was a box-office disappointment, it has developed a mystique as the last completed film by Gable and Monroe. It has been listed in the National Film Registry, formed by Congress to preserve films deemed "culturally, historically, or esthetically important." The movie inspired a documentary, The Making of the Misfits, for PBS.