Oral tolerance is a type of immune hypo-responsiveness induced by oral administration of food or harmless gastrointestinal antigens. It is evident that the induction of oral tolerance can protect our body from enteric problems, such as food allergies and colitis caused by autoimmunity. Here we review the immunological mechanisms of oral tolerance, the role of T cell cytokines in generating tolerance and the impact of Peyer's patches and mesenteric lymph nodes, and discuss the part played by commensal microflora in the regulation and maintenance of the intestinal barrier. The potential clinical applications of oral tolerance in human disease therapy are also included in this review. Understanding the mechanisms of oral tolerance may lead to the development of alternative strategies for preventing or suppressing the symptoms of autoimmune diseases and allergies.