It is now well known that immunoglobulin E (IgE) and mast cells (MCs) are important participants in allergic diseases. MCs contain electron-dense secretory granules which are filled with inflammatory mediators. The interaction of an allergen (antigen) with an antigen-specific IgE-bound high-affinity receptor for IgE (FcεRI) is an essential step in MC activation as well as subsequent downstream signaling events. What we know is that IgE and FcεRI activate a complex regulatory network ( i.e. , signaling molecules and messengers) that governs both the type of MC activation and the symptoms of allergic disease. This review focuses on recent discoveries that shed new light on FcεRI signaling networks, holding promise for the development of new therapeutic solutions in the treatment of allergic diseases.