Allergen-specific immunotherapy (AIT) has been implemented for more than 100 years, and achieves sustained unresponsiveness by administrating escalating doses of the causative allergen until a maintenance dose is reached. Immunotherapeutic protocols spanning different durations (from hours for ultra-rush protocols to weeks or months for conventional protocols) are applied for the treatment of food, pollen, pet dander and insect sting allergy. Desensitization takes place in sequential steps such as very early desensitization of mast cells and basophils, skewing of T- and B-cell responses towards regulatory phenotype, modulation of allergen-specific antibody isotypes and inhibition of migration and mediator release of eosinophils, basophils and mast cells.