Research on the mechanisms of immune regulation in allergy and asthma has shown substantial progress in recent years and has led to a variety of allergen-specific therapeutic and preventive approaches. Studies on the area of allergen-specific immunotherapy (allergen-SIT) have provided substantial knowledge on the mechanisms of allergic disease with novel developments for treatment and prevention. Several studies have demonstrated that increased numbers and the activation of allergen-specific T regulatory cells correlate with successful allergen-SIT. Particularly, targeting of the molecular mechanisms of immune tolerance and reciprocal regulation of effector and regulatory T-cell subsets are foreseen for the development of new strategies for immune intervention. This review focuses on current knowledge of immune tolerance to allergens in healthy immune response to allergens and allergen-SIT.