Mast cells are multifunctional effector cells of the immune system, capable of producing a variety of vasoactive mediators, cytokines and growth factors. The presence of resident mast cells in the myocardium has been established; however, their exact role in cardiac pathology remains unclear. The current review presents evidence suggesting the importance of mast cells in the infarcted myocardium. Myocardial ischemia and reperfusion results in degranulation of cardiac mast cells, and release of preformed inflammatory mediators, such as TNF-α and histamine in the ischemic area. Mast cell derived products may modulate endothelial gene expression and mononuclear cell cytokine synthesis. During the proliferative phase of healing, significant mast cell accumulation is noted in areas of fibrosis and myofibroblast proliferation. Stem Cell Factor (SCF), the obligate growth factor for mast cells, is induced in the healing myocardium. Mast cells may have an important role in scar formation through the secretion of growth factors and fibrogenic substances (such as TGF-β, basic FGF, tryptase and VEGF), that may promote collagen deposition and angiogenesis. Understanding the role of the mast cell in myocardial infarction is important in order to design site-specific pharmacological interventions that could mitigate inflammatory injury, without interfering with myocardial healing.