The gastrointestinal tract is the largest immunologic organ in the body. It is constantly bombarded by a myriad of dietary proteins. Despite the extent of protein exposure, very few patients have food allergies because of development of oral tolerance to these antigens. Once proteins contact the intestinal surface, they are sampled by different cells and, depending on their characteristics, result in different responses. Antigens might be taken up by Microfold cells overlying Peyer's patches, dendritic cells, or epithelial cells. Different cells of the immune system participate in oral tolerance induction, with regulatory T cells being the most important. Several factors can influence tolerance induction. Some are antigen related, and others are inherent to the host. Disturbances at different steps in the path to oral tolerance have been described in food hypersensitivity. In this review we provide an overview of oral tolerance and cite data related to food hypersensitivity wherever evidence is available.