Our understanding of the molecular and genetic etiologies of allergic disorders, which affect 20%-30% of the general population, has greatly improved over the past several years. Previously, research focused on examination of immediate hypersensitivity reactions, initiated by the cross-linking of IgE molecules on the surface of mast cells/basophils, resulting in the release of a host of mediators, which cause symptoms typified by acute anaphylaxis. Although there has been substantial progress in understanding the molecular biology of mast cell and basophil activation and of the regulation of IgE synthesis, recent studies have shifted attention to the cellular and molecular mechanisms that cause a broader allergic inflammatory response and underlie the more chronic and severe symptoms of allergy and asthma. In this report, we will review a substantial body of recent experimental work that has provided the basis for our new understanding of the allergic inflammatory response and the pathogenesis of allergic diseases. We will describe the recent progress in defining the immunological basis for allergic disease, and how subsets of helper CD4+ T cells secreting a specific array of cytokines (Th2 cytokines) regulate/cause allergic inflammation. We will review the cell biology of Th2 cells, the role of Th2 cells in allergic disease, and biological, genetic, and therapeutic mechanisms that influence the differentiation of CD4+ T cells and enhance or suppress cytokine synthesis in Th2 cells. These mechanisms control the expression of allergic diseases, which occur in some but not all individuals following environmental exposure to allergens.