INTRODUCTION

The advent of modern immunosuppressive therapy is arguably the single most important factor in allowing solid organ transplantation to progress from a dubious and dangerous venture to the treatment of choice for end-stage organ failure. During the past two decades, a broad array of immunosuppressants has emerged to expand the armamentarium used by transplant physicians and surgeons for prevention and treatment of organ allograft rejection. The availability of these drugs has resulted in steadily improved outcomes for kidney, kidney/pancreas, liver, heart, lung, pancreas, and intestinal transplants. It has also allowed for the development of clinically feasible protocols for multiorgan transplantation, as well as transplantation of pancreatic islets, gonads, and compound tissues such as limbs. Despite these remarkable successes immunosuppressive drugs continue to lack specificity and are associated with many acute and chronic side effects. Although there has been significant progress in understanding the mechanistic basis of immunological tolerance, consistent clinical application of this knowledge to allow graft-specific tolerance, the “Holy Grail” of transplantation, remains elusive. Thus, the large majority of organ transplant recipients in the current era continue to require lifelong immunosuppression. Among the agents in common worldwide use for this purpose are corticosteroids, a select number of small-molecule drugs, and a growing panel of so-called biological agents that includes monoclonal and polyclonal antibodies. In addition to these established agents, a number of novel immunosuppressants have entered preclinical and clinical trials in organ transplant recipients in recent years and show promise for broader clinical use in the near future.