To obtain a current understanding of the mechanisms, clinical indications, efficacy, and safety of sublingual immunotherapy (SLIT) for the treatment of children and adults with allergic rhinitis, asthma, and allergic conjunctivitis. A MEDLINE and Index Medicus search for peer-reviewed articles on SLIT was performed. Since the approval of SLIT by the World Health Organization in 1988, the efficacy and safety of SLIT have been confirmed in several new double-blind, placebo-controlled studies for monosensitized patients who are allergic to house dust mites, grass pollens, ragweed, and birch pollen. Documented immunologic responses to SLIT have included a decrease in serum eosinophilic cationic protein and interleukin 13 (IL-13) levels, an elevation in IL-12 levels, a reduction in late-phase responses, and increases in IgG4/IgE ratios. A Cochrane review of 22 studies confirmed the efficacy and safety of SLIT for patients with allergic rhinitis. A long-term asthma study showed sustained efficacy 5 years after discontinuing the vaccine. The safety of SLIT has been confirmed in postmarketing studies, and severe systemic adverse effects have never been reported. In view of its safety profile, SLIT is taken by the patient at home (away from specialized centers), and no specialized resuscitation facilities are required. SLIT is a safe and effective therapeutic option for patients with allergic rhinitis and asthma. Because of its efficacy, safety, and ease of administration, it has been accepted in Europe, Southern Africa, Australasia, Southeast Asia, and the Middle East as a promising therapeutic option that can significantly alter the natural history of allergic disease without the risks of injection immunotherapy.