Summary: Mast cells (MCs) are major effector cells of immunoglobulin E (IgE)-mediated allergic inflammation. However, it has become increasingly clear that they also play important roles in diverse physiological and pathological processes. Recent advances have focused on the importance of MCs in both innate and adaptive immune responses and have fostered studies of MCs beyond the myopic focus on allergic reactions. MCs possess a variety of surface receptors and may be activated by inflammatory mediators, IgE, IgG, light chains, complement fragments, proteases, hormones, neuropeptides, and microbial products. Following activation, they produce a plethora of pro-inflammatory mediators and participate in inflammatory reactions in many organs. This review focuses on the role of MCs in inflammatory reactions in mucosal surfaces with particular emphasis on their role in respiratory and gastrointestinal inflammatory conditions.