Allergen immunotherapy (AIT) is the only treatment able to act on the causes and not merely on the symptoms of allergy. AIT was introduced 100 years ago but remained an empirical treatment for more than 40 years, when the first controlled trial in 1954 opened the era of scientific evidence. A major advance was the introduction of venom immunotherapy to prevent anaphylaxis from insect stings in 1978. Concerning inhalant allergens, currently AIT may be administered in two forms, subcutaneous (SCIT), and sublingual immunotherapy (SLIT). A large number of trials, globally analyzed in a number of meta-analyses, gave sound evidence to the efficacy and safety of SCIT and SLIT in allergic rhinitis and asthma. Adverse systemic reactions are still a drawback for SCIT while safety and tolerability of SLIT are very good, provided recommended doses and schedules of administration are used A significant advance for SLIT development was the registration in Europe of the standardized quality tablets. New applications, such as food allergy and atopic dermatitis, as well as new routes of administration, are currently under evaluation. After 100 years of use, AIT has a central role in the management of allergy and the ongoing improvement seems able to warrant to AIT an even brighter future.