Sickle cell nephropathy is one of the main chronic complications of sickle cell disease (SCD), the most common of the hematological hereditary disorders. Several studies have been performed since the first description of SCD 100 years ago to investigate the mechanisms of kidney involvement in this disease. It has been demonstrated that both glomerular and tubular compartments can be damaged as a direct consequence of SCD, including renal function loss, concentration and acidification deficits, and glomerulopathies. This article highlights the aspects of sickle cell nephropathy pathophysiology and clinical manifestations and describes the most recent advances in the diagnosis and treatment of this disorder.