Recent advances in immunosuppression have focused on more effective, safer, and targeted therapies that have resulted in improved short- and intermediate-term renal allograft survival. During the past decade there has been a marked decrease in acute rejection rates following renal transplantation because of the use of newer immunosuppressive agents. Recent data indicate that the average yearly reduction in the relative hazard of graft failure beyond I year was 4.2% for all recipients (0.4% for those recipients who had an acute rejection episode and 6.3% for those who did not have an acute rejection). Despite these improvements the currently available immunosuppressive agents are associated with significant cardiovascular risk factors, an increased risk of infection, and the development of malignancies in the long term. Predictive parameters of donor-specific hyporesponsiveness are needed so as to allow identification of patients in whom immunosuppressive therapy can be safely reduced. Immunosuppressive agents that have recently been approved for use in the United Slates and those that are in clinical and preclinical studies are discussed.