Sickle cell disease is an autosomal recessive disorder and the most common genetic disease affecting African-Americans. Approximately 0.15% of African-Americans are homozygous for sickle cell disease, and 8% have sickle cell trait. Hemoglobin S polymerization leads to red cell rigidity, microvascular obstruction, inflammation, and end-organ ischemic injury. Our published data indicate that up to 50% of sickle cell patients have endothelial dysfunction due to impaired bioavailability of endogenous nitric oxide. Our studies indicate that this is due in large part to scavenging of nitric oxide by cell-free hemoglobin, with additional nitric oxide inactivation by superoxide. This suggests that therapies directed at restoring NO bioavailability might be beneficial. In patients with atherosclerotic vascular disease, the statin family of 3-hydroxy-3-methylglutaryl (HMG) CoA reductase inhibitors significantly reduce stroke and myocardial infarction and restore endothelial-dependent relaxation of conducting arteries. Furthermore, statin therapy has now been clearly shown to reduce C-reactive protein levels and clinical events in patients with coronary artery disease independent of the effects on lipoproteins. The ability of statins to correct vascular inflammation and endothelial dysfunction makes this class of agents attractive to attempt to reverse these features of sickle cell pathobiology. This trial will aim to 1) establish the effects of oral atorvastatin treatment on endothelial-dependent relaxation in patients with sickle cell disease and endothelial dysfunction; 2) establish the effect of therapy on peripheral blood markers of inflammation and vascular function, and peripheral blood proteome and transcriptome profiles; and 3) investigate whether superoxide produced through xanthine oxidase limits nitric oxide bioavailability in patients with sickle cell disease.