Since the early 1900s, allergen immunotherapy has been recognized as an effective treatment option for patients with inhalant allergies. Subcutaneous injection has traditionally been the main route of antigen delivery for immunotherapy in the United States. Over the past 15 years, sublingual administration of allergen extract has become a widely used method of immunotherapy in other countries, particularly in Europe. Although sublingual immunotherapy (SLIT) has been used by some physicians in the United States, this technique has not found widespread utilization. A growing interest in SLIT use in this country is developing. SLIT offers several potential advantages, including excellent safety and tolerability, increased access to immunotherapy, and improved method of antigen delivery to children. This paper reviews the basic and clinical science data available in the literature concerning the immunology, efficacy, and safety of SLIT. It is written to serve as a springboard for future discussions and clinical investigations regarding the potential expanded use of SLIT in the United States.