Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in the United States, and its prevalence is increasing worldwide. It currently affects approximately 30% of adults and 10% of children in the United States. NAFLD represents a wide spectrum of conditions ranging from simple fatty liver which in general follows a benign nonprogressive clinical course, to nonalcoholic steatohepatitis (NASH), which is a more serious form of NAFLD that may progress to cirrhosis and end-stage liver disease. At present, a liver biopsy remains the only reliable way to diagnose NASH and establish the presence of fibrosis. Current noninvasive clinically available tests lack accuracy and reliability. In light of the dramatic increase in the prevalence of NAFLD in conjunction with the significant research effort in developing novel therapies for patients with NASH, noninvasive, simple, reproducible, and reliable biomarkers are greatly needed. They will not only help in the diagnosis of NASH, but also be useful for assessment of treatment response and prognosis and remain a research priority in the NAFLD field.