Rheumatoid arthritis (RA) is a chronic disease of joints that is characterized by inflammation, abnormal cellular and humoral immune responses, and synovial hyperplasia. Mast cells (MCs) are involved in several of these inflammatory and immune events. MC-derived mediators induce edema, destroy connective tissue, and are involved in lymphocyte chemotaxis and infiltration and in pathological fibrosis of RA joints. Moreover, MCs are involved in angiogenesis during RA, and their proteolytic activity results in cartilage destruction and bone remodeling. Lastly, MCs could be a target in the treatment of RA.