Immunotherapy (IT) of IgE-mediated diseases has been used since its first description in 1911. This therapy has been used in patients with inhalant allergy and insect venom sensitivity. Unfortunately, IT suffers from the crudeness of the allergy extracts and the inability to define allergenic epitopes. Moreover, this form of IT has been increasingly questioned because of improvements in pharmacotherapy and the risks of untoward reactions. These untoward reactions even include anaphylaxis and death. Despite this criticism, there are increasing data on the efficacy of immunotherapy and considerable research is underway to improve the risk-benefit ratio of treatment. Other approaches directed at inhibiting the sequential events of both the afferent and efferent limbs of allergic reactions are in progress. This involves specific alterations of target cells, i.e., mast cells and basophils. Moreover, the development of recombinant allergens and the precise definition of the binding site of IgE will further promote research and development of new means of IT. Gene targeting therapy may follow, directed at T cells specific for allergen epitope(s) or IgE binding sites. The future holds great promise and excitement.