Several members of the chemokine family play an important role in reparative fibrosis and are involved in the pathogenesis of remodeling following myocardial infarction. Chemokines may regulate the fibrotic process through recruitment and activation of mononuclear cell subsets and fibroblast progenitors (fibrocytes), by exerting direct effects on resident fibroblasts, and by modulating angiogenesis. Monocyte Chemoattractant Protein (MCP)-1/CCL2 is the best studied chemokine in cardiac fibrosis. Disruption of the MCP-1 axis reduces fibrosis attenuating dilation of the infarcted ventricle. In addition, MCP-1 signaling is activated in response to insults that do not cause cardiomyocyte death, such as brief ischemia or pressure overload and regulates fibrous tissue deposition in experimental models of fibrotic non-infarctive cardiomyopathy. Understanding the role of chemokine-mediated interactions in the development of cardiac fibrosis may identify novel therapeutic targets for treatment of patients with heart failure.