Despite substantial advances in the treatment of acute myocardial infarction, ischemic cardiac injury and ventricular dysfunction may develop in patients undergoing reperfusion therapy. In the past few years, several experimental and clinical studies have investigated ways of enhancing myocardial salvage and regeneration. Although clinical evidence suggests that some treatment strategies might be able to enhance myocardial salvage and regeneration, many open questions remain, including the exact mechanisms leading to benefits, the influence of patient characteristics, optimal clinical indication and patient selection, and delivery method, route, and timing of therapies. Further clinical trials are needed to clarify these issues.