Allergies result from immune responses to environmental compounds (allergens), which are normally harmless agents on their own, derived from sources such as pollen, animal dander, and house mites. Allergens trigger disease through activation of inflammatory pathways in sensitized individuals, initiating immune defense mechanisms that are out of proportion to the allergen threat to the individual. The inflammation pathways are thought to involve the production of the IgE class of antibodies, which develop specificity for particular allergens. The IgE antibodies on their own are incapable of activating an immune response, which requires the interaction of these antibodies with specific cells carrying a high-affinity receptor for the antibody. IgE bound to the surface of cells acts as a sensitive sentry for the presence of small amounts of allergens. The recognition of allergens triggers the cellular receptors and the activation of these cells, which release histamines, leukotrienes, and other mediators of the allergic response. Recent studies have elucidated the atomic interactions between the antibodies and their high-affinity receptors that are at the heart of this inflammatory pathway, providing new tools to develop therapeutic treatments for allergies and asthma.