Allergen immunotherapy has been shown to be efficacious in numerous studies for the clinical indications of allergic asthma and rhinitis, as well as hymenoptera venom hypersensitivity. How allergen immunotherapy improves clinical symptoms is still not entirely clear. Decreases in specific IgE follow a complex cascade of effects: a shifting of the cytokine milieu from TH2 to TH1 predominance, with resultant decrease in interleukin 4, decreased recruitment and activation of eosinophils, and decreased proliferation of mast cells. Allergen exposure has a lessened ability to stimulate an inflammatory cell response, with decreased target organ hyperreactivity. Since allergen immunotherapy is not without risk, the decision needs to be made whether injection therapy is safe and provides benefit not achievable by medical management. The continued clarification of optimal allergen concentrations through careful studies of standardized extracts will allow better control of adverse events by limiting unnecessarily potent mixtures.