Animal and human research has established the beneficial effects of enteral nutrition on the gut. Both the innate and acquired immune systems are bolstered by enteral alimentation. Emerging clinical concepts tie these beneficial effects to a significant influence on the host immune response to stressors during critical illness. In this article, we examine how enteral nutrition impacts gastrointestinal immunity and demonstrate how these changes may affect the body's systemic immune response to nongastrointestinal challenges. This modulatory effect occurs because of changes in the pattern of cytokine secretion and alterations in lymphocyte and neutrophil recruitment. Imbalances in these regulatory mechanisms may be the engine driving hyperresponsiveness to subsequent challenges in the critically ill patient.