Focal segmental glomerulosclerosis (FSGS) is one of the major causes of nephrotic syndrome in adult as well as in the children. Untreated or steroid-resistant primary FSGS often shows a progressive renal insufficiency and reaches to end-stage renal failure. Concerning the treatment for such patients, the combined immunosuppressive therapy with corticosteroid and other cytotoxic drugs (cyclophosphamide, cyclosporine and tacrolimus etc.) is recommended. Since podocyte injury seems to be the most important primary events in FSGS, the extensive studies have been focused on the role of podocyte-related molecules. Recently slit membrane-associated molecules (CD2AP, alpha-actinin 4 and podocin) and angiotensin II type I receptor in the podocyte have been clearly shown to be relevant for the pathogenesis of FSGS.