Renal transplantation has matured over the past nearly half-century to become an accepted means of treating end-stage renal disease. Despite innovations in surgical technique and organ preservation, immunosuppressive therapy continues to be the limiting factor in the long-term survival of renal allografts. Some controversy still exists regarding the need for induction protocols in clinical renal transplantation, and even more so as to the optimal means for induction. Since its advent in the early 1980s, most of the maintenance immunosuppressive regimens have revolved around the cornerstone of cyclosporine. New agents recently approved for clinical use and those currently in development may be in a position to replace older agents (for example, tacrolimus [FK506] in place of cyclosporine, mycophenolate mofetil for azathioprine). Unlike cyclosporine, some of these agents (eg, tacrolimus, mycophenolate mofetil, and a new parenteral agent 15. deoxyspergualin) have the added advantage that they are effective in reversing ongoing (and sometimes even steroid-resistant) episodes of acute rejection. To show clinical superiority, however, these new agents will have to demonstrate clinical utility for prevention of chronic rejection, the major limiting factor in long-term renal allograft survival. New clinical regimens employing early protocol biopsies to predict which patients are at risk for chronic renal allograft rejection may allow some of the newer agents to be tested in clinical trials in a prospective, randomized manner. Regardless of their clinical utility, however, the current financial climate may dictate that the ultimate fate of many of these newer agents will depend on pharmacoeconomic considerations.