Non-alcoholic fatty liver disease (NAFLD) is common and may progress to end-stage liver disease. Liver-related morbidity and mortality occur almost exclusively in patients whose disease progresses to advanced fibrosis and cirrhosis. Presence and severity of liver fibrosis seem the most important indicators of long-term prognosis. Clinical and biochemical variables may help select NAFLD patients in whom liver biopsy may provide the most prognostic information. Some serum markers of liver fibrosis and imaging techniques aimed at measuring liver stiffness are under investigation as tools to determine severity of liver fibrosis in patients who have NAFLD, but none of them yet can replace liver biopsy.