The outcome of multiply injured patients has been significantly improved by the establishment of definitive treatment protocols. These algorithms are constructed of phases that place priorities on the various diagnostic and therapeutic modalities. The only lifesaving skeletal intervention that is necessary during the resuscitative phase is pelvic clamp placement on an unstable pelvic ring in a patient with massive retroperitoneal bleeding. In the primary operative phase, the condition of the soft tissues dictates the emergent nature of extremity injuries. Special attention is drawn to the critical patient with severe thoracic injury or severe head trauma. Experimental data suggest that early intramedullary nailing of femur fractures leads to additional trauma due to pulmonary fat embolization and a systemic inflammatory response. Clinical retrospective and prospective studies do not support these research findings, however. Patients with closed head injury may benefit from early surgery, provided that hypotension, excessive fluid administration, and hypoxia do not occur intraoperatively. Primary unreamed intramedullary nailing of the femur is a safe and appropriate technique and is recommended, but prudent reamed nailing, elastic plate osteosynthesis, and temporary external fixation remain valuable alternatives. In the second operative phase, secondary soft tissue and osseous reconstruction of preliminarily stabilized injuries is undertaken. This includes the exchange of initial external fixators as well as open reduction and internal fixation of periarticular fractures. In the tertiary phase, delayed osseous and soft tissue reconstruction occurs. The eventual functional outcome of a multiply injured patient is dependent up appropriate early stabilization and delayed reconstruction of the musculoskeletal system.