As Mayo Clinic celebrates its 500th heart transplant, cardiologists and transplantation specialists Brooks S. Edwards, M.D., and Sudhir S. Kushwaha, M.D., review advances in the treatment of end-stage heart failure, including ventricular assist devices and immunosuppressive strategies, and discuss when a transplant should be considered with Charanjit S. Rihal, M.D., Mayo Clinic cardiologist.