Food antigens may play an important role in the etiology of a variety of gastrointestinal conditions ranging from food allergy and malabsorption syndromes to inflammatory bowel disease. However, the prevailing terminological confusion relative to allergy in the last years and in particular on the definition and classification of adverse reactions to foods joined to the absence of definitive diagnostic tests have impeded the investigation of food-allergic reactions. In the last few years the development of animal models and its application to the clinical ground have brought about new light to the mechanisms that regulate the response to antigenic challenge. In particular, the better understanding of the participation of key cellular elements, such as mast cells and basophils, in the modulation of immediate hypersensitivity reactions and the demonstration of the existence of IgE-independent immunologic mechanisms, have rendered new insights for diagnosis and treatment of food allergy.