The simultaneous dysfunction of several organs (MODS, or multiple organ dysfunction) represents the most challenging task for the intensivist. In recent rears more and more patients have been diagnosed as suffering from MODS due to several causes, including better immediate treatment of injuries that only a few years ago would have been considered incompatible with life or with consequent reduced organ reserve. Even if initially MODS has been associated with infections and sepsis, because of its similarity with a generalized inflammatory reaction mediated by a wide array of mediators, it is now clear that noninfectious insults, such as multiple trauma, acute pancreatitis, and retroperitoneal bleeding, can start a chain reaction ultimately leading to the onset of MODS. A specific trigger factor has not yet been identified, but experimental and clinical evidence suggests that the gut, endothelium, and immune sl stem interact to produce the altered metabolic and cardiorespiratory patterns commonly observed in patients with MODS. It is thus possible that a target-oriented approach, including rapid correction of intestinal underperfusion, supply Of specific nutrients, and downregulation of the inflammatory cascade, can act as either a preventive measure for subjects at risk pr as a main treatment for patients with full-blown MODS.