The complement system is an important immediate host defense mechanism after trauma, extensive burn injury and after invasion by microbial pathogens. Massive complement activation, however, seems to be detrimental and may contribute further to the disease process and eventually to multiple organ failure or the septic state. In clinical situations in which complement is damaging, the logical therapy should be, if at all possible, the removal of the activated complement components from the circulation. However, much of the protein is attached to the membrane and effective locally, so prevention of the enzymatic cascade may be more appropriate. There has been little progress in manipulating the complement system to effectively alter such disease processes caused by the clinical situations and there is an important need for further research in the field.