Immunotherapy has its roots in the advances of immunology, which occurred at the end of the 19th and the beginning of the 20th century. The original, incorrect concept was that allergic rhinitis and conjunctivitis were caused by toxins released by pollen particles. It was believed that protective antibody, or antitoxin, would develop when subjects with these diseases were vaccinated, or immunized, with pollen vaccines. Behring and Kitasato introduced this concept by inducing protection from diphtheria and clostridia bacterial toxins.

The evolving concept of anaphylaxis, beginning with Portier and Richet in 1902, and astute clinical observations of human allergic disease directed investigators to conclude that the mechanism responsible for clinical allergy is a hypersensitivity reaction, not exposure to exogenous toxins. Immunotherapy is a form of immunomodulation that decreases the hypersensitivity response to allergens. During the succeeding decades, the clinical experience and majority of clinical trials attest to the efficacy of immunotherapy.