Since 1983, cyclosporine has been the backbone of immunosuppression in clinical organ transplantation. Cyclosporine is usually used in combination with steroids and with another second-line immunosuppressant like azathioprine or mycofenolate mofetil. With these regimens, graft survival at 1 year exceeds 90% and long-term results are excellent. The main complication is renal toxicity, which is usually secondary to excessive exposure. The new microemulsion formulation of cyclosporine, introduced in recent years, has improved intestinal absorption and bioavailability and resulted in much less intrapatient variation than the older formulation. The introduction of 2-hour peak blood level monitoring, which corresponds closely to the area under the curve of the drug, allows more appropriate dosing, thus minimizing rejection owing to underexposure or toxicity owing to overexposure. As new effective immunosuppressants are currently becoming available for use in combination with cyclosporine, the transplant community can look forward to more effective and safer immunosuppression.