Severe sepsis with associated multisystem organ dysfunction is a leading cause of death in patients hospitalized in intensive care units. The gastrointestinal system plays a key role in the pathogenesis of multisystem organ dysfunction owing to a breakdown of intestinal barrier function and increased translocation of bacteria and bacterial components into the systemic circulation. During critical illness, alterations occur in gut microflora owing to several factors, including changes in circulating stress hormones, gut ischemia, immunosuppression, the use of antibiotics, and lack of nutrients. The importance of endogenous strains of probiotic bacteria such as Bifidobacterium and Lactobacillus in maintaining intestinal barrier function and also in modulating mucosal and systemic immune responses is becoming evident from numerous studies. Bacteria in synbiotic (prebiotic and probiotic combinations) and probiotic (mutistrain combinations) preparations are being used experimentally in the treatment of acute pancreatitis, liver transplantation, and in trauma patients. Recent studies have shown treatment of patients with multiple trauma or acute pancreatitis with synbiotic preparations resulted in reduced rates of infection, sepsis, and mortality in patients. Enterally fed patients in the intensive care unit treated with a probiotic compound demonstrated enhanced immune function and decreased incidence of diarrhea. Results from these clinical trials are encouraging, and warrant further investigation to clarify which probiotic bacterial strains are of most benefit to this population.