Despite significant effort devoted to developing new treatments and procedures, cardiac disease is still one of the leading causes of death in the world. The loss of myocytes due to ischemic injury remains a major therapeutic challenge. However, cell-based therapy to repair the injured heart has shown significant promise in basic and translation research and in clinical trials. Embryonic stem cells have been successfully used to improve cardiac outcomes. Unfortunately, treatment with these cells is complicated by ethical and legal issues. Recent progress in developing induced pluripotent stem cells (iPSCs) using non-viral vectors has made it possible to derive cardiomyocytes for therapy. This review will focus on these non-integration-based approaches for reprogramming and their therapeutic advantages for cardiovascular medicine.