Extremity wounds compose the burden of injury in the global war on terrorism, and there is a great need for research to improve the treatment of soldiers who incur these devastating injuries. The mission of the United States Army Institute of Surgical Research is to conduct combat casualty care research in several areas, including explosive injury mechanisms, field tourniquet use, external fixator pin coating, wound irrigation optimization, antibiotic-impregnated bone graft substitutes, segmental muscle defects, and outcomes research. Future research directions include development of bone and soft-tissue regenerative technologies, prevention and treatment of heterotopic ossification, and bacteriology of unique pathogens.