In the nearly 30 years since the first successful human heart transplant, a variety of developments have allowed this form of cardiac replacement therapy to flourish. These have included improvements in surgical and critical care technology, as well as breakthroughs in immunosuppressive pharmacology, the most notable of which was the introduction of cyclosporine in 1980. Subsequently, indications and exclusion criteria for heart transplantation have evolved, guided by the constraints of a limited donor supply and facilitated by an improved understanding of prognostic risk factors. Current 1- and 5-year survival estimates are encouraging, and despite the frequency of acute rejection, current management strategies have, for the most part, limited the fatal consequences of this complication. Graft atherosclerosis, however, has continued to complicate the posttransplant course of many patients, and despite therapeutic strategies aimed at a variety of potential pathogenic mechanisms, this entity remains the most common cause of late death after transplantation. In these patients and other victims of allograft failure, retransplantation remains a viable option. Finally, the recent trend of selecting increasingly critically ill transplant recipients, although not associated with inferior survival, has driven the costs of this form of cardiac replacement therapy to unprecedented levels. These issues, as well as current developments in the fields of mechanical cardiac assistance, xenotransplantation, and cardiac gene therapy, will certainly result in a continually evolving role for cardiac transplantation in the treatment of end-stage heart disease.