Clinical application of heart transplantation goes beyond 25 years experience. The main indications for cardiac transplantation remain idiopathic cardiomyopathies and ischemic diseases. To obtain a suitable donor has become progressively more difficult due to the increase of transplants performed and the shortage of donors. Advances in the detection of early rejection, improved organ preservation procedures, and the introduction of new immunosuppressive therapy protocols have produced dramatic results in heart transplantation. Late graft atherosclerosis remains a serious threat despite retransplantation and, in some cases, mechanical cardiac support.