BACKGROUND: Critically ill patients are susceptible to injury of the intestinal mucosa, changes in gut permeability, and failure of intestinal defense mechanisms. These conditions put the patients at risk for infection and multiple organ dysfunction syndrome. Specific therapies are needed to prevent gut failure during critical illness. OBJECTIVE: The purpose of this literature review is to provide a better understanding of the normal defense mechanisms of the gut and alterations associated with ischemia-reperfusion injury, risk of infection, and the link to multiple organ dysfunction syndrome in critically ill patients. Implications for early enteral stimulation and nutrition are included. METHODS: Medical and nursing studies on the intestinal response to critical illness and on the implications for early enteral nutrition in critically ill patients were reviewed. RESULTS: Significant advances have been made in understanding the normal defense mechanisms of the gut, including barrier and immune functions. Translocation of bacteria, mediators of the inflammatory response, and the microcirculation play a role in the response to critical illness. Enteral nutrition that includes glutamine and arginine enhances gut function and improves patients' outcomes in some clinical states. DISCUSSION: Further research should focus on specific strategies to enhance gut function, prevent loss of gut integrity, and improve patients' outcomes. These strategies include maintaining mesenteric blood flow, using gastric tonometry to assess oxygenation, inhibiting inflammatory mediators, and using growth factors to modify the metabolic state in patients who are critically ill.