Cocaine Cowboys chronicles the development of the illegal drug trade in Miami during the 1970s and 1980s with interviews of both law enforcement and organized crime leaders, in addition to news footage from the era.

The logistics involved included the purchase and financing of legitimate businesses to provide cover for illegal operations, the use of sophisticated electronic homing devices, and other elaborate transportation schemes.

Importers reveal that condominiums were purchased near particular ocean waterways to provide a monitoring post for U.S. Coast Guard and local police patrol boats, and high-tech radio equipment was used to monitor the radio frequencies of federal, state, and local authorities in order to warn incoming boats and airplanes.

Later, when law enforcement pressure drove many major players out of the picture, numerous high-end stores and businesses closed because of plummeting sales.

The interviewees in the film argue that Griselda Blanco, an infamous crime family matriarch, played a major role in the history of the drug trade in Miami and other cities across America.