Despite the development of effective immunosuppressive therapy, transplant graft arterial disease (GAD) remains the major limitation to long-term graft survival. Multiple immune and nonimmune risk factors contribute to this vasculopathic disease process; the interplay between host inflammatory cells and donor endothelial cells results in an intimal hyperplastic lesion, whereas alloantigenindependent factors such as prolonged ischemia, surgical manipulation, ischemia-reperfusion injury, and hyperlipidemia may enhance antigen- dependent events, leading to ischemia and graft failure. Several studies suggest that the 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors, or statins, exert cholesterol-independent immunosuppressive effects beyond their original lipidlowering effects. Clinical studies demonstrate that statins reduce GAD in human cardiac allografts, improving chances for survival, although it remains unclear whether this is secondary to cholesterol-lowering or other mechanisms. Further studies will provide a firm rationale for using statins in organ transplantation.