The introduction of cyclosporine (CsA) into clinical practice resulted in a dramatic reduction in the incidence and severity of acute rejection. As a result, short-term and medium-term kidney allograft survival increased greatly. However, the long-term patient and graft survival have not improved to a similar degree. This can partly be attributed to the side effects of CsA and partly to the fact that the use of CsA has not led to a reduced incidence of chronic allograft nephropathy. Thus, there has been a continuing search for strategies that minimize CsA toxicity but maintain adequate immunosuppression. This has resulted in the development of the CsA microemulsion formulation and improved methods for therapeutic drug monitoring. With the introduction of newer immunosuppressive drugs, early CsA withdrawal and CsA-free immunosuppressive therapy have become feasible. However, CsA weaning or complete avoidance is associated with a slightly higher risk of acute rejection, and the long-term efficacy and safety of such strategies remain to be established. Therefore, it is to be expected that in the near future CsA will remain part of the standard immunosuppressive regimen in many transplant centers.