Therapeutic drug monitoring of cyclosporine has been established as part of the routine clinical treatment for patients after organ transplantation. The inability to define optimal dose (maximize efficacy/minimize toxicity) has been a problem related to drug monitoring of cyclosporine. The original cyclosporine formula showed high intra-patient and inter-patient variability and low bioavailability. The microemulsion formulation of cyclosporine (Neoral) was introduced to address the absorption problems related to the original cyclosporine formulation. With the introduction of Neoral, renewed interest in methods of therapeutic drug monitoring brought us from trough monitoring (C0) to levels measured 2 hours after dosing (C2). The pharmacokinetic rationale for using C2 to monitor patients receiving Neoral has demonstrated a reduced incidence of rejection in de novo patients and improvements in safety profile in both renal and hepatic transplant recipients. Monitoring C2 levels is a more precise method for optimizing cyclosporine dosing and a better way to individualize therapy. Further data are required from prospective trials to evaluate the clinical benefits of adopting C2 monitoring in cardiac and lung transplant recipients as well as in long-term maintenance patients.