The landmark Randomized Evaluation of Mechanical Assistance in the Treatment of Congestive Heart Failure (REMATCH) trial demonstrated that the implantation of left ventricular assist devices (LVADs) as an alternative to heart transplantation, or destination therapy (DT) is superior to any known medical therapy in patients with end-stage heart failure who are not eligible for transplantation. In this article, we review results of the first United States and European clinical trials of DT, including the REMATCH, the Investigation of the Non-Transplant Eligible Patients who are Inotrope Dependent (INTREPID), and the Clinical Utility Baseline Study (CUBS) trials, as well as the outcomes of the first DT implantations in the post-REMATCH era in the United States. The article summarizes the current state of knowledge and future directions in the field of permanent mechanical circulatory support therapy as an alternative to heart transplantation.