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Although the number of available donor hearts severely limits the epidemiologic impact of heart transplantation on patients with heart failure, patients with end-stage heart failure unresponsive to medical management currently have no other viable alternatives. Destination therapy with a ventricular assist device is the closest toward approaching clinical reality but has been plagued with problems of infection and stroke. The purpose of this review is to summarize recent developments in the field that may broaden the clinical impact of heart transplantation. For example, novel methods of cardiac preservation are being designed to safely evaluate and utilize “extended criteria” donors. Surgical techniques and medical management have reduced the incidence of postoperative right heart failure, and immunosuppressive regimens promise to limit chronic graft vascular disease.