Interleukin 4 (IL-4) mediates important pro-inflammatory functions in asthma, including T helper cell type 2 lymphocyte differentiation, induction of IgE production, up-regulation of IgE receptors, expression of vascular cell-adhesion molecule 1, promotion of eosinophil transmigration into the lungs, inhibition of T-lymphocyte apoptosis, and mucus hypersecretion. The role of IL-4 in the pathogenesis of asthma is supported by identification of polymorphisms linked to asthma in the IL-4 gene promoter and proteins involved in IL-4 signaling. Several approaches to IL-4 antagonism are or have been in clinical development. This article examines IL-4 and the antagonists that have been developed. Early trial results and the future of anti–IL-4 therapy are discussed.