Mast cells have long been recognized as the critical tissue-based effector cells in IgE-mediated allergic diseases. Ligation of the high-affinity receptor for IgE (FceRI), constitutively expressed on mast cells, promotes cell activation and immediate release and production of pro-inflammatory mediators. Besides these positive signals, FceRI aggregation has recently been understood to generate negative intracellular signals capable of limiting mast-cell functional responses. This review is aimed at providing a summary of the mechanisms through which FceRI engagement can generate negative signals and regulate mast-cell function. Similar mechanisms are employed by other receptors expressed by immune cells, such as T cell and B cell receptors, pointing to a general concept in negative immunoreceptor signaling.