In recent years, bacterial translocation from the gut onto pancreatic necrosis has been proposed as the main cause of pancreatic infection and the consequent sepsis. Failure of the intestinal barrier, together with bacterial overgrowth due to motility changes and immunosuppression, constitute the pathways of the continuous pancreatic contamination from bacterial translocation in patients with severe acute pancreatitis. Selective decontamination, by using a combination of oral and intravenous antibiotics, has been reported to decrease the incidence of sepsis and the related mortality. Immunostimulation is another action to be taken to enhance the ability of the immune system to prevent bacterial translocation, by the entrapment and killing, by enterocytes, of the bacteria trying to translocate through the bowel wall. To keep the mucosal barrier function intact is one of the main issues in the prevention of bacterial translocation. This could be achieved by the adequate delivery of oxygen and nutrient supplementation. Enteral nutrition is a key factor, as it has been proven to maintain mucosal integrity, along with preventing deterioration of the immune function of the intestine.