Immune privilege in the gut is the result of a complex interplay between the gut microbiome, gut luminal antigens, and the intestinal epithelial barrier. Composed of both physical and immunochemical components, the intestinal barrier secretes immunoregulatory mediators that promote the generation of tolerogenic antigen‐presenting cells, phagocytic innate immune cells characterized by ‘inflammatory anergy’, and regulatory cells of the adaptive immune system. Innate immune cells mediate controlled transepithelial transport of luminal antigens as far as the mesenteric lymph nodes, where the intestinal and peripheral immune systems intersect. This promotes the generation of adaptive regulatory lymphocytes that actively suppress effector cell responses against gut luminal antigens and flora. The net result is the generation of tolerance to dietary antigens and the maintenance of gut homeostasis. Dysregulation of this complex immunoregulatory network leads to diseases such as food allergy and inflammatory bowel disease. Future therapies for these diseases will likely involve the functional restoration of the barrier and regulatory cell functions at the epithelial/luminal interface.