Objective To review major milestones in the development of subcutaneous allergen immunotherapy in 20-year segments. Data Sources Review of the literature available in textbooks and journals. Study Selection Articles and books addressing major achievements in the development of subcutaneous allergy immunotherapy were selected for inclusion in this review. Results Immunotherapy administration has improved the lives of possibly millions of patients with hay fever. Asthmatic symptoms have been relieved if not ablated in millions as well. Insect venom hypersensitivity became treatable and highly effective. In the beginning years of immunotherapy, it was clear that immunotherapy worked; in the later years, the mechanisms for this efficacy were discovered. In this case, the therapy preceded its validation. Methods, materials, and safety have vastly improved. Postulated mechanisms explain much but not everything. Conclusions There is still research to be accomplished, improvements to be made, and, of course, patients to be made well.