The aggregation of high-affinity IgE receptors (Fc epsilon RI) on mast cells and basophils has long been known as the critical event that initiates allergic reactions. Monomeric IgE was recently found to induce a variety of effects when binding to Fc epsilon RI. Upregulation of Fc epsilon RI only requires binding, whereas other responses require Fc epsilon RI aggregation. Interestingly, Fc epsilon RI aggregation has recently been understood to generate a mixture of positive and negative intracellular signals. Mast cells and basophils also express low-affinity and, under specific conditions, high-affinity IgG receptors. When co-engaging these receptors with Fc epsilon RI, IgG antibodies can amplify or dampen IgE-induced mast cell activation. On the basis of these findings, it has been proposed that FcRs can be used as targets and/or tools for new therapeutic approaches to allergies.