Acute myocardial infarction remains a leading cause of death worldwide. Despite reperfusion strategies, patients who survive the initial ischemic event are at a higher risk for development of heart failure from a process referred to as ventricular remodeling. After the initial ischemic event, an intense inflammatory response is observed, mainly characterized by infiltration of pro-inflammatory monocytes. Early post-infarction remodeling is characterized by a biphasic cellular response — an acute pro-inflammatory phase that includes recruitment of inflammatory cells (neutrophils, very early) followed by pro-inflammatory Ly6Chigh monocytes, and a second subacute phase involving the recruitment of reparative, alternatively-activated Ly6Clow cells that resolve the inflammatory response and initiate tissue replacement and myocardial repair. The prevailing hypothesis holds that proinflammation response is responsible for the progression of heart disease. However, current clinical trials of anti-inflammatory therapies have failed to show benefit in heart failure patients. We summarize recent advances in our understanding of the role of pro-inflammatory and anti-inflammatory macrophages in tissue repair which may help to develop effective therapeutics to control cardiac diseases.