The first several seasons imagined protagonist Johnny Dollar as a private investigator drama, with Charles Russell, Edmond O'Brien and John Lund portraying Dollar in succession over the years. In 1955 after a yearlong hiatus, the series came back in its best-known incarnation with Bob Bailey starring in "the transcribed adventures of the man with the action-packed expense account – America's fabulous freelance insurance investigator." There were 809 episodes (plus two not-for-broadcast auditions) in the 12-year run, and more than 710 still exist today. Jim Cox's book American Radio Networks: A History cites "886 total performances" which includes repeat performances.

Format.

The format best remembered was instituted by writer-director Jack Johnstone. Each case usually started with a phone call from an insurance adjuster, calling on Johnny to investigate an unusual claim: a suspicious death, an attempted fraud, a missing person, or other mysterious circumstances. Each story required Johnny to travel to some distant locale, usually within the United States but sometimes abroad, where he was almost always threatened with personal danger in the course of his investigations. He would compare notes with the police officials who had first investigated each strange occurrence, and followed every clue until he figured out what actually happened. Johnny's file on each case was usually referenced as a "matter," as in "The Silver Blue Matter" or "The Forbes Matter". Later episodes were more fanciful, with titles like "The Wayward Trout Matter" and "The Price of Fame Matter" (the latter featuring a rare guest-star appearance by Vincent Price as himself; here Price and Dollar team up to retrieve a painting stolen by Price's insurance agent).

Johnny usually stuck to business, but would sometimes engage in romantic dalliances with women he encountered in his travels; later episodes gave Johnny a steady girlfriend, Betty Lewis. Johnny's precious recreational time was usually spent fishing, and it was not uncommon for Johnny's clients to exploit this favorite pastime in convincing him to take on a job near good fishing locations. His past was rarely mentioned, but Dollar in “The Bennett Matter” described himself as a four-year US Marine veteran who then worked as a police officer for a decade before changing careers to insurance investigation. In "The Blackburn Case" Dollar also refers to his time as a Pinkerton Detective.

Each story was recounted in flashback, and every few minutes the action would be interrupted by Johnny listing a line item from his expense account, which served as an effective scene transition. Most of the expense account related to transportation, lodging, and meals, but no incidental expense was too small for Johnny to itemize, as in "Item nine, 10 cents. Aspirin. I needed them." The monetary amounts weren't always literal: the smallest line item Johnny ever recorded was "two cents: what I felt like" after a professional setback; the largest was "one million dollars" (the way he felt after finding a missing woman and her daughter in a snowbound cabin). The episodes generally finished with Johnny tallying up his expense account and traveling back to Hartford, Connecticut, where he was based. Sometimes Johnny would add a sardonic postscript under "Remarks," detailing the aftermath of the case. ("The Todd Matter," which especially disgusted Johnny, ended abruptly with "Remarks – nil!")

In later seasons the program sometimes referred to itself, with other characters recognizing Dollar's voice from the radio; in the episode “The Salkoff Sequel Matter” Johnny’s radio show becomes an important plot point.