While the incidence of nephrotic syndrome (NS) is decreasing in Korea, the morbidity of difficult-to-treat NS is significant. Efforts to minimize treatment toxicity showed that prolonged treatment after an initial treatment for 2-3 months with glucocorticosteroids was not effective in reducing frequent relapses. For steroid-dependent NS, rituximab, a monoclonal antibody against the CD20 antigen on B cells, was proven to be as effective, and short-term daily low-dose steroids during upper respiratory infections reduced relapses. Steroid resistance or congenital NS are indications for genetic study and renal biopsy, since the list of genes involved in NS is lengthening.