Heart failure is the leading cause of death worldwide, due to the limited capacity of the adult heart to regenerate. Today, the treatment of heart failure is based on the use of devices, pharmacological therapy of symptoms, and heart transplantation. However, these approaches do not represent a long-term solution and the availability of heart donors is inadequate. For this reason, there is great interest in regenerative medicine to treat heart failure. This review summarizes primary strategies of cardiac regenerative medicine, their present status, and future perspectives and challenges.