The gastrointestinal tract and the generalized inflammatory response initiated by severe injury or infection have been implicated in the pathophysiology of multiple-organ system failure. Once multiple-organ system failure has occurred, treatment focuses on supporting end-organ function. Recent studies have shown, however, that it may be possible to reduce the incidence and prevalence of multiple-organ system failure by controlling the reperfusion injury cascade, normalizing gastrointestinal blood flow and preserving the integrity of the gastrointestinal immune barrier.