The use of cyclosporine (CyA) in clinical thoracic transplantation has markedly improved the survival and quality of life of patients in the past 2 decades. In the mid-1990s a significant advance in formulation design took place with the introduction of Neoral. This new microemulsion formulation of CyA demonstrates reduced intersubject and intrasubject variability in absorption and improved oral bioavailability compared with the oil-based CyA formulation. Moreover, C2 measurements of CyA could result in an even better method to avoid overimmunosuppression. On the other hand, generic alternatives of CyA could potentially reduce costs to transplant recipients as well as to the general community. Since the initiation of tacrolimus, mycophenolate mofetil, and rapamycin, slow but expanding variations of immunosuppressive protocols have taken place. Transplantation medicine is thus becoming an increasingly exciting and innovative field, in which CyA continues to play a central role as the core immunosuppressant of choice for the majority of patients.