Allergic inflammation is initiated by the contact between allergen(s) and specific IgE antibodies, driven by regulatory cells such as antigen presenting cells and T lymphocytes, which orientate and orchestrate the response, and sustained by effector cells such as mast cells, basophils, and eosinophils. Among tissues and organs targeted by allergy, the nose, the lungs and the skin have the property to spread in distant sites the initially local reaction, thus resulting in systemic disease. By contrast, the oral mucosa seems to be a tolerogenic site regarding the immunologic response to allergens. This mucosa is characterized by abundance of dendritic cells, which are antigen presenting cells specialized in uptaking, processing and presenting the antigens to T cells, and particularly to T regulatory cells which in turn can downregulate Th1 and Th2 immune responses by direct cell contact or by production of immunosuppressive cytokines. The other important aspect of the oral mucosa is the negligible presence of effector inflammatory cells, namely mast cells and eosinophils, which accounts for the reportedly good safety of sublingual administration of allergen immunotherapy. These peculiar aspects and patents have important implications in treatment and prevention of allergic diseases.