The disturbances of gut barrier in critically ill patients may influence their outcome and prognosis. Experiments in animals show that fasting and stress collaborate to produce intestinal atrophy and translocation of microorganisms and toxins. This fact is one of the main arguments to promote the use of early enteral feeding in critically ill patients. However, the intestinal barrier behaves differently in humans than in animals. The human enteral cells have a good tolerance to fasting and stress, mucosal atrophy is mild and it is not always associated with changes in intestinal permeability. Moreover, the relationship between intestinal permeability with sepsis and bacterial translocation is controversial. This last phenomenon also happens in normal subjects and may be a mechanism to build immunological memory. One of the most important factors that influence bacterial translocation is the microorganism, that under stress conditions can adhere to the intestinal cell and penetrate the intestinal barrier. Splanchnic ischemia and reperfusion is one of the main pathogenic factors in the failure of intestinal barrier. Finally, the fact that the small bowel is an inflammatory target of extra intestinal injuries, explains several clinical situations. The pathophysiology of the intestinal barrier definitely requires more research.