During the past 20 years, major advances have been made in understanding the molecular and cellular mechanisms of allergen tolerance in humans. The demonstration of T cell tolerance, particularly that mediated by the immune-suppressive functions of IL-10, led to a major conceptual change in this area. Currently, the known essential components of allergen tolerance include the induction of allergen-specific regulatory subsets of T and B cells, the immune-suppressive function of secreted factors, such as IL-10 and TGF-β, the production of IgG4 isotype allergen–specific blocking antibodies, and decreased allergic inflammatory responses by mast cells, basophils, and eosinophils in inflamed tissues.