Orthopedic injuries suffered by casualties during combat constitute approximately 65% of the total percentage of injuries and are evenly distributed between upper and lower extremities. The high-energy explosive injuries, environmental contamination, varying evacuation procedures, and progressive levels of medical care make managing combat-related injuries challenging. The goals of orthopedic injury management are to prevent infection, promote fracture healing, and restore function. It appears that 2% to 15% of combat-related extremity injuries develop osteomyelitis, although lower extremity injuries are at higher risk of infections than upper extremity. Management strategies of combat-related injuries primarily focus on early surgical debridement and stabilization, antibiotic administration, and delayed primary closure. Herein, we provide evidence-based recommendations from military and civilian data to the management of combat-related injuries of the extremity. Areas of emphasis include the utility of bacterial cultures, antimicrobial therapy, irrigation fluids and techniques, timing of surgical care, fixation, antibiotic impregnated beads, wound closure, and wound coverage with negative pressure wound therapy. Most of the recommendations are not supported by randomized controlled trials or adequate cohorts studies in a military population and further efforts are needed to answer best treatment strategies.