The introduction of cyclosporine into clinical practice improved transplant outcome. However, the use of cyclosporine is not without problems. A narrow therapeutic index (the drug causes irreversible kidney damage when given in too high a dose) coupled with variable absorption and unpredictable pharmacokinetics has resulted in the need to measure cyclosporine blood concentrations to enable the dose of the drug to be individualised to the patient. When this is done correctly therapeutic efficacy can be maximised while toxicity is kept to a minimum. The evolution of cyclosporine dose optimisation started with the adjustment of empirical fixed doses by clinical "judgement;" progressed to therapeutic drug monitoring of trough, predose, C0 concentration with non specific assays that measured parent drug and metabolite; then on to "specific" cyclosporine C0 measurements; through area under curve monitoring using full profile measurements and limited sampling scheme procedures; and finally ending up with absorption profiling that targets AUC in the first 4 hours or the 2 hour blood cyclosporine concentration, C2. At the same time the formulation of cyclosporine has changed from Sandimmune to Neoral and now generic forms of the latter are available. The evidence base supporting C2 monitoring continues to grow and the technique will need to be customised as new combination therapies emerge. Therapeutic drug monitoring of cyclosporine may also need to be tailored to avoid the potential negative impact of switching patients to generic forms of the drug.