The complex pathophysiology of sickle cell disease (SCD) is remarkably similar to that observed in other chronic vascular diseases and involves multiple biologic pathways triggered by ischemia reperfusion injury, coagulation activation, and inflammation. Statins are potent lipid-lowering agents commonly used to reduce the risk of cardiovascular disease. Independent of their lipid lowering effect, statins have been shown to down-regulate inflammatory mediators and endothelial adhesion molecules, reduce tissue factor expression and restore nitric oxide bioavailability. The pleiotropic effects of statins make these agents attractive therapeutic candidates for SCD. This article reviews available evidence for the potential role of statins in SCD. Pediatr Blood Cancer 2013; 60: 550–557. © 2012 Wiley Periodicals, Inc.