Cyclosporine is a critical dose drug for which individualisation by therapeutic drug monitoring is indisputable. Current evidence suggests that a single concentration (C2) taken two hours after cyclosporine administration with the microemulsion formulation better predicts exposure and events than the trough concentration (C0), which is routinely used for adjusting the dosage of this drug. Studies have shown that the greatest calcineurin inhibition and the maximum inhibition of IL-2 production occur in the first 1 to 2 hours after dosing. These findings support the concept that the C2level better reflects immunosuppressive efficacy than the trough concentration. Preliminary data from an outcome study in liver transplant recipients have shown that the incidence of biopsy proven moderate to severe acute rejection was significantly lower in patients managed by C2monitoring compared with those monitored by C0. The critical importance of achieving adequate cyclosporine exposure during the first 3 to 5 posttransplant days to prevent acute rejection has been documented in prospective studies with de novo renal and liver transplant recipients. Conversion of maintenance liver and heart transplant patients to C2monitoring resulted in an amelioration of renal function. Time-dependent target values have been proposed for liver and renal transplant recipients. These require further prospective validation. For routine monitoring of C2levels on-site validated dilution guidelines are necessary for most of the available immunoassays. C2monitoring necessitates further organizational requirements which may be judged differently between transplant centers. In particular during the early posttransplant period C2monitoring is a promising new option to make immunosuppressive therapy with the microemulsion formulation of cyclosporine safer and more efficient.