Since 1977, the cardiac transplantation program at Columbia has performed 2143 heart transplant operations with a current 1-year survival rate of approximately 87% and a 5-year survival rate of approximately 76%, representing the largest single-institution experience in North America. Over three decades of experience in the selection of donors and recipients has permitted us to expand eligibility limits and relax conventional exclusion criteria, allowing us to transplant high-risk donors and medically complex recipients with excellent results. Increasing use of mechanical support is being seen to bridge candidates to cardiac transplantation. Recipient characteristics, rather than those of the donor, substantially impact outcome following OHT and use of extended-criteria donors helps to alleviate the ongoing donor shortage; but this scarcity of donor hearts remains the major obstacle to the growth of transplantation. During the last decade, substantial improvements have been made in the areas of immunosuppression, treatment of rejection, and handling of sensitized recipients. Frequent causes of late mortality such as graft rejection, infection and TCAD, have been significantly diminished in the modern area of immune manipulation but remain major causes of death and barriers to long-term survival.