During the past 20 years, cyclosporine (CsA) has become the main part of immunosuppressive protocols. Its impact to improve the quality and quantity of transplantation surgery has been enormous. Immunosuppression in allograft recipients 10 years after renal transplantation CsA continued to demonstrate benefits on graft survival without evidence of long-term morbidity. The pharmacokinetic properties of CsA show wide interpatient variation. After being subject of intense investigation for more than 20 years, it only recently has the full potential of the drug been realized, primarily due to two advances: first, the development of a microemulsified formulation, (Neoral), that improves drug delivery; second, substantial improvements in CsA monitoring. Sparse-sampling algorithms were developed specifically to predict AUCs. We prospectively investigated the practicality, intrapatient variability, and impact on the outcomes of toxicity and rejection episodes using an algorithm. Rejection episodes were diminished by 43.5% in the first 3 months compared to the results in the previous 3 years. Furthermore, the relation of the trough versus C2 concentrations performed at day 3 to 5 and 10 to 12 predicted the probability of an acute rejection episode. Using a truncated AUC to identify patients at risk for rejection episodes early provides optimal and individualized immunosuppression. This pharmacokinetic rationale has now eventuated in an international consensus statement that represents a further step toward optimal immunosuppression.