Management of combat-related trauma is derived from skills and data collected in past conflicts and civilian trauma, and from information and experience obtained during ongoing conflicts. The best methods to prevent infections associated with injuries observed in military combat are not fully established. Current methods to prevent infections in these types of injuries are derived primarily from controlled trials of elective surgery and civilian trauma as well as retrospective studies of civilian and military trauma interventions. The following guidelines integrate available evidence and expert opinion, from within and outside of the US military medical community, to provide guidance to US military health care providers (deployed and in permanent medical treatment facilities) in the diagnosis, treatment, and prevention of infections in those individuals wounded in combat. These guidelines may be applicable to noncombat traumatic injuries under certain circumstances. Early wound cleansing and surgical debridement, antibiotics, bony stabilization, and maintenance of infection control measures are the essential components to diminish or prevent these infections. Future research should be directed at ideal treatment strategies for prevention of combat-related injury infections, including investigation of unique infection control techniques, more rapid diagnostic strategies for infection, and better defining the role of antimicrobial agents, including the appropriate spectrum of activity and duration.