Primary focal segmental glomerulosclerosis (FSGS) is the representative of refractory nephrotic syndrome in both adults and children. We review the clinical course and predictors of renal outcome in adult FSGS. Patients resistant to treatment frequently develop end-stage renal disease (ESRD), whereas patients achieving a remission show an excellent outcome. The renal survival rate in Japanese patients is 68.7% in 10 years and 31.4% in 20 years, indicating a better prognosis compared with the previous studies. When clinical and histological features at presentation have been evaluated by multivariate analysis, serum creatinine concentrations (>1.5 mg/dl) and the presence of tubulo-interstitial lesions (>20%) are significant positive predictors of progression to ESRD. We also discuss treatment for adult FSGS, with emphasis on intensive and prolonged therapy.