Corticosteroids represent the first therapeutic approach for patients with focal and segmantal glomerulosclerosis. What to do in patients who do not respond to corticostetoids is still uncertain. Cytotoxic agents have been tried. The results are usually poor when these drugs are given for short periods but almost half of patients may enter remission ir treatment is prolonged. Some decrease in proteinuria may be obtained with mycophenolav, mofetil but the available reports are still scanty and the follow ups are short. Cyclosporine has been largely used both in controlled and non controlled trials with favorable results. However, being the drug nephrotoxic caution should be recommended with its use. Plasma-exchange and lipopheresis may attempted in resistant cases.