IgE-dependent activation of mast cells is central to the allergic response. The engagement of IgE-occupied receptors initiates a series of molecular events that cause the release of preformed, and de novo synthesis of, allergic mediators. Recent investigations demonstrate a critical role for non-enzymatic proteins that facilitate the activation and coordination of biochemical signals required for mast cell activation. Among these LAT, SLP-76 and Gab2 are critically important as adapters that facilitate events initiated by IgE receptor-dependent activation of Src family protein tyrosine kinases, Lyn and Fyn. An evaluation of the role of these adapters points to complementary but independent steps in early signaling and the possibility that preference for one or another adaptor complex may result in selective mast cell responses.