Burns are a very real component of combat-related injuries, and infections are the leading cause of mortality in burn casualties. The prevention of infection in the burn casualty transitioning from the battlefield to definitive care provided at the burn center is critical in reducing overall morbidity and mortality. This review highlights evidence-based medicine recommendations using military and civilian data to provide the most comprehensive, up-to-date management strategies for initial care of burned combat casualties. Areas of emphasis include antimicrobial prophylaxis, debridement of devitalized tissue, topical antimicrobial therapy, and optimal time to wound coverage. This evidence-based medicine review was produced to support the Guidelines for the Prevention of Infections Associated With Combat-Related Injuries: 2011 Update contained in this supplement of Journal of Trauma.