Cirrhosis and chronic liver failure are leading causes of morbidity and mortality in the United States, with the majority of preventable cases attributed to excessive alcohol consumption, viral hepatitis, or nonalcoholic fatty liver disease. Cirrhosis often is an indolent disease; most patients remain asymptomatic until the occurrence of decompensation, characterized by ascites, spontaneous bacterial peritonitis, hepatic encephalopathy, or variceal bleeding from portal hypertension. Physical examination of patients with cirrhosis may reveal a variety of findings that necessitate a hepatic- or gastrointestinal-based work-up to determine the etiology. Some patients already may have had laboratory or radiographic tests that incidentally uncovered signs of cirrhosis and its comorbidities. No serologic or radiographic test can accurately diagnose cirrhosis. A significant correlation has been demonstrated between persistently elevated liver function tests and biopsy-proven underlying hepatic disease; thus, a more targeted serologic work-up is indicated in patients whose liver function test results are persistently abnormal. Unnecessary medications and surgical procedures should be avoided in patients with cirrhosis. Referral for liver biopsy should be considered only after a thorough, non-invasive serologic and radiographic evaluation has failed to confirm a diagnosis of cirrhosis; the benefit of biopsy outweighs the risk; and it is postulated that biopsy will have a favorable impact on the treatment of chronic liver disease.