Abnormal results of standard biochemical liver tests occur frequently; however, the prevalence of clinically significant liver disease is only about 1% in all patients screened. Thus, development of a rational and cost-effective approach to these patients is important. Liver diseases are generally classified as hepatocellular, cholestatic, and infiltrative. Cholestatic liver disease is further categorized as intrahepatic and extrahepatic. Hepatocellular disease is characterized by transaminase increases greater than 5 times the upper limit of normal, with alkaline phosphatase levels usually increased less than 2 to 3 times the upper limit of normal. Cholestatic disease is characterized by an increase in the alkaline phosphatase level that is 3 to 5 times greater than the upper limit of normal, with only a mild increase of transaminases. The exception to this is cholestasis with cholangitis when the transaminases can be more substantially increased. In infiltrative diseases of the liver such as lymphoma or granulomatous hepatitis, the alkaline phosphatase level is increased disproportionately to that of the bilirubin. Specific etiologic diagnoses cannot usually be based on routine biochemical liver test results, and thus more specialized serum tests are necessary. A liver biopsy is often needed for a precise diagnosis in patients with long-term increases in liver test results. Ultrasonography is the best initial imaging technique for the liver, and if biliary dilatation is noted, endoscopic retrograde cholangiopancreatography is recommended.