That the gastrointestinal tract performs important immunologic, metabolic, and barrier functions, in addition to nutrient digestion and absorption, has recently become clear, as have the potential deleterious consequences of loss of mucosal barrier function. Because of the potentially important relationship between nutrition and gut barrier function, this area has received increasing clinical and experimental attention over the past several years. Consequently, this review focuses on how nutrition can modulate the integrity of the gut mucosal barrier. Special attention will be given to the biology of normal intestinal barrier function, as well as to studies investigating the role of nutritionally related variables on the gut mucosal barrier.