Protocols for antibiotic prophylaxis in the treatment of fractures caused by gunshots have not been delineated clearly in the literature to date. The current review of the literature reveals that antibiotic therapy for treatment of these fractures is predicated on the muzzle velocity of the weapon used to inflict the fracture. General consensus has been reached regarding the requirement of at least 24 hours of intravenous antibiotic treatment in fractures caused by high-velocity weapons in conjunction with the appropriate wound and fracture care. Similarly, in fractures caused by shotguns, thorough wound debridement and 24- to 48-hour administration of intravenous antibiotics is necessary. However, in fractures caused by low-velocity weapons, there is not a preponderance of the evidence showing that there is a distinct advantage to using antibiotic prophylaxis in these injuries. Special clinical consideration must be given regarding the use of antibiotics in fractures caused by gunshots that are intraarticular and those about the hand, foot, and ankle.