The incidence of ESRD continues to increase, particularly in older populations, and is associated with considerable comorbidity and a diminished QOL. Renal replacement therapy has been shown to improve QOL in patients with ESRD, and renal transplantation appears to produce greater improvements in QOL than dialysis. In the years since the first transplantations, the techniques have progressed from experimental to a practical approach to the treatment of end-stage solid organ failure. Substantial advances that have improved both short-term and long-term patient and graft survival have led to a heightened awareness of the need to examine the long-term QOL in transplant recipients. Recent trends show that patients are less concerned with short-term outcomes, such as whether a renal allograft will be lost, and more concerned with anxieties about long-term kidney function and overall health. Side effects associated with immunosuppression in transplantation can impact QOL negatively. The availability of newer immunosuppressants offers the possibility that these agents might be used to improve efficacy and decrease side effects associated with traditional agents, thereby improving QOL. However, healthcare systems will also insist that therapeutic regimens be cost-effective. Much work remains to evaluate new immunosuppressive regimens, although limited early results suggest sirolimus is a promising agent.