Sublingual immunotherapy (SLIT) for allergic respiratory diseases was first described in 1986 and immediately appeared as a viable alternative to the traditional subcutaneous route. Since then, more than 60 randomized controlled trials have been published, almost all with very favorable results. The average improvement over placebo in symptom score and medication use was always greater than 20%. The results of the clinical trials were pooled in several meta-analyses, which consistently confirmed the efficacy of the treatment. SLIT is characterized by a satisfactory safety profile, its side effects being mainly limited to oral discomfort. Only six anaphylaxes and no fatalities have been so far reported. Due to the good risk:benefit ratio, SLIT is currently being investigated in diseases other than respiratory allergy, such as food allergy and atopic dermatitis.