The prevalence of heart failure is increasing, and the prognosis of end-stage heart failure remains dismal. The gold-standard therapy in end-stage heart failure remains cardiac transplantation at the present time, but there is a great excess of eligible candidates compared with the number of donor organs. Advances in mechanical support, the development of the left ventricular assist device (LVAD), and the total artificial heart has reduced mortality and morbidity in patients awaiting transplantation, and LVADs are now approved as an strategy for destination therapy. Miniaturization, increased device durability, and complete implantability may render LVADs an option in earlier stages of heart failure, as a bridge to myocardial recovery or even as a viable alternative to transplantation. Alternative strategies under investigation are cell therapy and xenotransplantation. In the present article, current and potential future therapeutic options in end-stage heart failure are reviewed.