Multiple organ failure (MOF) stems from a complex interaction between the host's immune response and inadequate tissue perfusion. Prevention of MOF therefore addresses these two components. The risk of inflammation is reduced through treatment of any infection and early stabilization of traumatized regions. Adequate respiratory and cardiocirculatory resuscitation is achieved to restore and maintain tissue perfusion. Although a supranormal cardiac output is often indicated, it is difficult to define precise endpoints for hemodynamic stabilization. Instead of increasing the oxygen supply to supranormal values in all patients, it is probably safer and more effective to increase it only in those patients for whom persistent ischemia is suspected. Provision of adequate nutritional support is important, and whenever possible the enteral route is preferred. Once MOF has developed, treatment turns to support of individual organs. Unfortunately, there is no single treatment for MOF that seems to reverse the associated trend of high mortality. Survival is more likely when the cause of MOF can be found and eliminated.