Immune tolerance - the adaptation of the immune system to external antigens or allergens - might be therapeutically manipulated to restore normal immunity in conditions such as allergy, asthma and autoimmune diseases. The field of allergen-specific immunotherapy is experiencing exciting and novel developments for the treatment of allergic and autoimmune diseases, and recent insights into the reciprocal regulation and counter-balance between different T-cell subsets is foreseen to facilitate new strategies for immunointervention. This Review highlights current knowledge of immunomodulatory therapies for the manipulation of immune tolerance and highlights recent approaches to improve allergen-specific immunotherapy for the treatment of allergic diseases.