Recent developments in sickle cell disease include the concept of a vasculopathic state and the classification of sickle cell disease into a hemolysis-endothelial dysfunction phenotype or a viscosity-vasoocclusion phenotype. The hemolysis-endothelial dysfunction phenotype largely reflects deficiency of or resistance to nitric oxide. In addition to discussing these areas, we suggest that the hemolysis-endothelial dysfunction phenotype also reflects the instability of sickle hemoglobin, the release of heme, and the induction of heme oxygenase-1. From these perspectives the renal complications of sickle cell disease are discussed and classified.