BACKGROUND: Specific immune response to allergens is decisive in the development of clinically healthy or allergic states. OBJECTIVE: Recent developments in the mechanisms of allergen-specific peripheral tolerance can be used for future treatment modalities. METHODS: This review focuses on recent developments in allergen tolerance. RESULTS/CONCLUSION: The balance between allergen-specific IL-10-secreting T regulatory cells (Tr1) and T helper 2 (Th2) cells appears to be decisive in the development of allergic and healthy immune response against allergens. Induction of IL-10- and TGF-beta-producing Tr1 cells, IgG4-isotype-blocking antibodies, and suppressed mast cells, basophils and eosinophils represent major components of a relatively normalized immune response after allergen-specific immunotherapy and healthy immune response to aeroallergens in sensitized individuals.