Specific immunotherapy (SIT) is the only treatment able to modify the natural history of the allergic subjects. Several aspects of the immunopathological response modified by SIT have been investigated; the first parameter historically studied was the production of allergen-specific antibodies. An increase of allergen-specific IgG4 and a decrease of IgE appear after SIT. A shift from Th2-polarized immune response toward Th1-oriented pattern has been reported after SIT. More recently, a crucial role for a subpopulation of T cells has been evidenced: T regulatory cells (Treg). Allergic patients have a defect of Tregs. SIT is able of inducing a specific Treg response. Sublingual immunotherapy is an alternative route of administration for SIT. Recent evidence shows that SLIT is also able of inducing a Treg response as detected by IL-10 production.