Based on the delicate balance between protection and harm, the posttraumatic inflammatory response has been rightfully termed a "double-edged sword" [40] [41] [42] . The present review will outline the current understanding of complement activation and regulation after major trauma, with a focus on specific injury patterns, including musculoskeletal trauma, ischemia/reperfusion, chest and brain injuries. We will furthermore discuss potential new pharmacological strategies related to the targeted inhibition of complement, which may shed some hope into the design of new immunomodulatory treatment modalities for severely injured patients in the future.