The default response of the mucosal immune system to antigens derived from food is one of active immune tolerance carried out by regulatory T cells and induced by dendritic cells residing in the intestinal mucosa. This tolerance response must be inhibited or bypassed to generate allergic sensitization in experimental food allergy and this has been achieved by 3 main approaches: genetic modifications, experimental adjuvants, and bypassing oral tolerance by administering the antigen through alternative routes. This article discusses the implications of these approaches for understanding the mechanisms of sensitization to food allergens in human disease.