Since beginning cardiac transplantation in 1985, Duke University Medical Center has performed 485 de novo heart transplants in adult recipients. Our program has broadened the access of patients to transplantation through the aggressive use of ventricular assist devices as bridge to transplant in patients with acute heart failure and shock, as well as through the introduction of an alternate list program for suboptimal transplant candidates. Despite this broadening of the recipient pool, our long-term outcomes have remained good, with 5-year survival of 75% and 10-year survival of 51%. Continued advances in immunosuppression and treatment for cardiac allograft vasculopathy seem likely to continue to improve long-term outcomes from cardiac transplantation. Expanding indications for VAD support (such as destination therapy) and continued improvements in this technology seem certain to impact patient selection and therefore the results of transplantation in the future. Appropriate triage of patients with advanced heart failure among available therapies will be the cornerstone of optimizing outcomes in this critically ill patient population.