The interaction of immunoglobulin E (IgE) and its receptors is critical for the manifestation of allergic disease. Currently, IgE receptors include the high-affinity Fc epsilonRI and the low-affinity Fc epsilonRII. Fc epsilonRI is a tetrameric or trimeric complex, and each has distinct expression patterns and unique functional consequences. In general, serum levels of IgE regulate Fc epsilonRI expression, and novel therapies that lower the concentration of IgE have provided insights into the contribution of this receptor in allergic disease. Newer therapies targeting Fc epsilonRI-signaling elements and the low-affinity IgE receptor, Fc epsilonRII (CD23), are being developed.