Cyclosporine, a potent immunosuppressive agent used to prevent rejection of transplanted organs, has a narrow therapeutic range and various toxic effects, mostly concentration-dependent. The kinetics of this drug present a large intra- and interindividual variability due to many factors, resulting in marked variations of blood cyclosporine concentrations, and in a poor correlation between administered dose and concentration. The knowledge of cyclosporine peculiarities and of factors affecting blood concentrations can provide a rational basis for establishing an adequate therapy for the individual patient. Cyclosporine monitoring is a method of evaluating whether the therapeutic choice is correct. Cyclosporine concentrations can be measured in whole blood, plasma, and serum using radioimmunoassay (RIA), high-performance liquid chromatography (HPLC) or fluorescein polarization immunoassay (FPIA). Different results are obtained, depending on the technique and on the biological fluids used. Cyclosporine measurement presents many problems and difficulties. There is a need for standardization and for quality assessment programs. The recent development of monoclonal antibodies may represent a significant advance for cyclosporine monitoring. Therapeutic drug monitoring (TDM) should be undertaken on a regular basis after the initiation of therapy with cyclosporine.