In contrast to mast cells and basophils, the high affinity IgE receptor (FcΕRI) on antigen-presenting cells (APC) shows structural and functional differences. It consists only of a minimal structure of one α- and two γ-chains and enables APC to efficiently take up and present antigen in IgE-mediated delayed-type hypersensitivity reactions that are thought to play a pivotal role in atopic diseases. However, recent studies of FcΕRI signal transduction and function on APC suggest additional mechanisms by which FcΕRI engagement on APC could affect inflammatory reactions. FcΕRI ligation is able to induce major signaling events like protein tyrosine kinase activation including p72syk leading to PLC-γ1 phosphorylation and consecutive calcium influx. Late signaling events like the activation of transcription factors such as NF-ĸB provide a link to the release of proinflammatory cytokines and chemokines, Th-polarizing factors such as IL-12 and the induction of antiapoptotic factors. FcΕRI-mediated IL-10 production in monocytes could also influence their differentiation. Since there are hints that in vivo a functional FcΕRI signaling pathway only exists in individuals from an atopic background, we suggest that these unexpected mechanisms may have an effect on inflammatory reactions in atopic diseases.