Major advances in the understanding of the immunologic process responsible for organ or cellular transplant rejection, a dramatic improvement in available immunosuppressive drugs, development of more sophisticated surgical techniques, and important progress in posttransplant intensive care over the last 30 years have led to a remarkable improvement in success following organ transplantation. Whereas excellent short-term survival of most transplanted organs is readily achieved, graft loss because of chronic rejection and the worsening problem of organ donor shortage remain major concerns in the field of transplantation. Recent advances in immunosuppressive drugs, induction of immunologic tolerance, and gene therapy strategies may help to prolong organ allograft survival in the future. Revised criteria for organ donation and xenotransplantation may one day solve the problem of organ supply. Today, as we approach the next millennium, we are optimistic that the elusive goal of immunologic tolerance will be achieved and perhaps applied to animal tissue. Such will certainly be the challenge for the next century.