BACKGROUND Nephrotic syndrome (NS)affects 2 every 100,000 children younger than 16 years. Minimal change disease (MCD) accounts for around 90 percent of cases and most of the remaining ones are associated with focal segmental glomerulosclerosis (FSGS). Patients with NS are at increased risk for life-threatening infections and thromboembolic episodes, and are often affected by dyslipidemia and osteoporosis. Glucocorticoids are first-line treatment and may achieve remission in about 90% of patients with MCD and in 20 to 60% of those with FSGS. In about 20% to 60% of those achieving remission, however, steroid withdrawal is followed by a recurrence of the disease. These patients require chronic steroid therapy (steroid-dependent cases): this prevents relapses in most cases but is invariably associated with severe adverse effects including growth retardation, infections, malignancies, hypertension, impaired glucose tolerance, weight gain and somatic changes. In a small proportion of patients, recurrences occur even under chronic steroid therapy (multirelapsing cases). In these cases, several approaches have been used to control disease activity including plasmapheresis and add-on therapy with cyclophosphamide, cyclosporine, mycophenolate mofetil and other immunosuppressants. Chronic immunosuppression, however, seldom achieves persistent remission and is invariably burdened by serious adverse effects including gonadotoxicity and sterility, opportunistic infections, malignancies, bone marrow depression and renal toxicity. Thus, safer and more effective treatments are urgently needed for these patients.