Cyclosporine A (CsA) was introduced to pediatric renal transplantation more than 20 years ago, and it has greatly improved graft survival and made transplantation the treatment of choice for children with end-stage renal failure. Exposure to CsA was shown to be highly variable among transplant recipients. Therefore, major efforts have been employed to monitor CsA blood levels. The widely used trough levels had never been formally validated, and every center had defined its own target values. With the advanced microemulsion formula of CsA, drug exposure became more predictable, but scientifically evaluated monitoring concepts are still lacking. Monitoring the absorption phase using single time points (eg, 2 hours after ingestion) is promising, as shown in adult trials. In pediatric transplant recipients, randomized clinical trials have to be implemented urgently to fully exploit the potential of CsA in the prevention of graft rejection while minimizing toxicity. Although newer immunosuppressive drugs have been developed, further studies should be undertaken to define the role of CsA in combination protocols.