Non-alcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease in the United States. It is considered the hepatic manifestation of the metabolic syndrome. Approximately a third of adults in the United States have NAFLD. While the majority of individuals with NAFLD do not develop progressive liver disease and have been classified as having non-alcoholic fatty liver (NAFL), a subset of patients with NAFLD have the progressive form termed non-alcoholic steatohepatitis (NASH) that may progress to cirrhosis, and hepatocellular carcinoma. Liver biopsy evaluation is the gold standard for the detection of NASH. It is impractical, unnecessary and cost prohibitive to subject all patients with NAFLD to a liver biopsy evaluation. Here in this review, we discuss our approach to clinical risk stratification of patients with NAFLD and who should be referred for a liver biopsy based upon the likelihood of finding the presence of NASH and/or advanced fibrosis on liver biopsy.