The Dalton brothers (Joe, Jack, William, and Averell) are imprisoned in Nevada Penitentiary under the watchful eye of warden Melvin Peabody. They repeatedly devise escape plans, taking advantage of weaknesses in the security system or opportunities presented to them. Their freedom and their return to a life of crime are their ultimate goals. However each successful escape is short-lived. They find themselves either back to the penitentiary or other prison-like environments. The Daltons' daily lives are further complicated by a group of recurring characters, such the dim-witted guard dog Rantanplan, sexy librarian Miss Betty, eccentric witch-doctor Fabulous Falcon, and tribal chief Crazy Wolf. Sometimes they help out the Daltons, and sometimes they hinter their plans.