Focal segmental glomerular sclerosis (FSGS) is the most common primary glomerular disease, resulting in heavy proteinuria and leading to ESRD. The term FSGS refers to a morphologic pattern of injury rather than a distinct disease. Sclerotic lesions are present in <50% of all glomeruli on light microscopy (hence focal), with <50% of the glomerular tuft affected (hence segmental). FSGS can be primary or secondary to a variety of physiologic, anatomic, or environmental factors. Primary FSGS is characterized by rather acute onset of heavy proteinuria, with other features of the nephrotic syndrome, renal impairment, and resistance to treatment in many patients.