Allergen specific immunotherapy, together with drugs and allergen avoidance, is a cornerstone in the management of respiratory allergy. The traditional subcutaneous route is burdened with the risk of severe adverse events; therefore, safer routes of administration (noninjection or local routes) have been investigated and developed. Controlled trials failed to demonstrate the clinical efficacy and the safety of oral and bronchial administration, and these routes have been abandoned. Local nasal immunotherapy proved effective and safe in 17 of 18 controlled trials; thus it is considered a viable route of immunotherapy. Nevertheless, nasal immunotherapy is effective in rhinitis only and requires a particular administration technique; therefore its use is slowly declining. The sublingual route is supported by numerous controlled trials showing its efficacy in asthma and rhinitis in adults and children. The safety profile, assessed in clinical trials and postmarketing surveillance studies, is satisfactory; the most frequent side effects are gastrointestinal complaints, which can be easily managed by proper dose adjusting. Sublingual immunotherapy is now accepted by the World Health Organization as a valid alternative to the subcutaneous route also in children. Although the long-lasting efficacy has been recently documented for the sublingual route, several points still need to be elucidated, including mechanisms of action, optimal dosage, cost-effectiveness, and adherence.