The spectrum of nonalcoholic fatty liver disease (NAFLD) starts from simple steatosis that can progress to nonalcoholic steatohepatitis (NASH), fibrosis, and cirrhosis. Importantly, patients with NASH and fibrosis are considered a high-risk group for liver and cardiac-related morbidity and mortality. The diagnostic evaluation of patients with NAFLD usually starts with the assessment of an asymptomatic patient with abnormalities in liver injury tests (most commonly elevation of aminotransferases) or referred for evaluation of liver steatosis incidentally found on abdominal imaging performed for other clinical reasons. Most of these patients have components of the metabolic syndrome (obesity, hypertension, hyperlipidemia, diabetes). Liver sonogram and blood tests to rule out other etiologies of liver disease, as well as a detailed history of alcohol intake, are essential to establish the diagnosis. Because of their significantly different clinical outcomes, from a prognostic stand-point, it is very important to establish the distinction between simple steatosis and NASH with or without fibrosis. The three noninvasive diagnostic tests that have been independently validated compared with liver biopsy for diagnosis of NASH and fibrosis are serum levels of CK-18 for diagnosis of NASH and ultrasound elastography and NAFLD fibrosis score for the diagnosis of advanced fibrosis. Serum biomarkers that have been validated (NAFLD fibrosis score, FibroTest) could be used as screening tools in patients with metabolic syndrome. Imaging techniques have been developed and could have a more widespread use in the future, but only ultrasound elastography has been validated extensively. CK-18 is a direct serum biomarker that could be part of the routine diagnostic evaluation for NASH in the near future. Routine tests appear to be more accurate than nonroutine tests for prediction of NAFLD and advanced fibrosis.