Two potential outcomes of dysregulated immunity are allergy and autoimmunity. Both are characterized by localized inflammation that leads to the injury and/or destruction of target tissues. Until recently, it was generally accepted that the mechanisms that govern these disease processes are quite disparate; however, new discoveries suggest that the mast cell may underlie much of the pathology in both these disease syndromes. Amongst these discoveries is the observation that mast cell-deficient mice exhibit significantly reduced disease severity compared to wild-type littermates in a murine model of multiple sclerosis (MS) and drugs that block mast cell function can improve clinical symptoms in this model. In addition, gene microarray analysis has revealed that the expression of several mast cell-specific genes is increased in the central nervous system plaques of MS patients. Although well established as effector cells in allergic inflammation, the location of mast cells and the wealth of inflammatory mediators they express make it likely that they have profound effects on many other autoimmune processes.