During the past 40 years, solid-organ transplantation has evolved into a routine clinical procedure for the management of end-stage heart, kidney, liver and lung disease as well as diabetes mellitus. This has mainly been accomplished through advances in understanding the molecular mechanisms involved in the rejection of allografts which has led to major improvements in immunosuppressive therapy. The discovery of the immunosuppressive drug cyclosporine which came into clinical use in the early eighties, revolutionized the field of transplantation. The short-term survival of allografts is now excellent but relentless loss of grafts over time due to chronic rejection remains a major problem. A number of complications can affect transplant recipients, most of which result from intensive immunosuppressive treatment. Among those are life-threatening infections and malignancies. The key issues concerning long-term management of transplant recipients are discussed.