Nonalcoholic fatty liver disease is a common cause of chronic liver disease in the general population. Nonalcoholic steatohepatitis (NASH), the aggressive form of nonalcoholic fatty liver disease, is associated with an increased risk of liver-related mortality and cardiovascular disease. At present, a liver biopsy is the only generally acceptable method for the diagnosis of NASH and assessment of its progression toward cirrhosis. Although several treatments have shown evidence of efficacy in clinical trials of varying design, there are no approved treatments for NASH, and published trials are often too divergent to allow meaningful comparisons. There is thus a lack of established noninvasive, point-of-care diagnostics and approved treatment on one hand and a substantial population burden of disease on the other. These provide the rationale for developing consensus on key endpoints and clinical trial design for NASH. Conclusion: This article summarizes the consensus arrived at a meeting of the American Association for the Study of Liver Diseases on the key endpoints and specific trial design issues that are germane for development of diagnostic biomarkers and treatment trials for NASH. (HEPATOLOGY 2011;54:344-353) N onalcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease in most of the Western world. [1][2][3] The clinical-histologic phenotype of the disease extends from nonalcoholic fatty liver to nonalcoholic steatohepatitis (NASH). NASH can progress to cirrhosis 4 and is also associated with an increased risk of cardiovascular mortality and type 2 diabetes mellitus. 5,6 Cirrhosis due to NASH increases the risk of hepatocellular carcinoma and NASH contributes substantially to the population burden of hepatocellular cancer. [7][8][9] There are many uncertainties in the diagnostic approaches, evaluation, and management of NASH. The diagnosis currently requires a liver biopsy, which is invasive, somewhat painful, and may be associated with life-threatening complications in some individuals. 10 Also, whereas several drugs have shown efficacy in clinical trials of varying design, [11][12][13] there are