One of the first police shows on radio, Gang Busters was the creation of actor and producer Phillips H. Lord, who had envisioned a hard-hitting show that would counteract the gangsterism that had made inroads into America in the 1920s and early '30s. The show began as G-Men in 1935 until Lord renamed the series and focused on presenting true crime stories "in cooperation with police and federal law enforcement departments throughout the United States."

The show began with one of radio's most famous openings, one so loud and active that the term "coming on like gangbusters" was coined in response. Each show concluded by describing the capture of wanted criminals and a series of "Gang Busters clues," with information about those who were still at large. By the early 1940s, it was reported that nearly 300 such criminals had been brought to justice thanks to Gang Busters.

Lord was the show's first narrator but was later replaced by Colonel H. Norman Schwarzkopf (who had been superintendent of the New Jersey State Police during the investigation of the Lindbergh baby kidnapping) and New York City Police Commissioner Lewis J. Valentine. This influential show closed its last case on November 27, 1957.

Gang Busters was inducted into the Radio Hall of Fame in 2011.