Since the advent of highly active antiretroviral therapy, liver disease has been a major cause of morbidity and mortality in patients with human immunodeficiency virus (HIV) infection. Chronic viral hepatitis accounts for >80% of liver-related mortality. Liver-related morbidity is due to acceleration of hepatitis C virus (HCV) disease, drug-induced hepatotoxicity, and, possibly, direct damage from HIV infection itself. As a consequence of this complex interaction, end-stage liver disease and hepatocellular carcinoma are frequent complications in patients with HIV infection. Infectious diseases physicians who care for HIV-infected patients with advanced HCV-related liver disease need to know how to assess for advanced fibrosis, to know when to refer a patient for endoscopic screening for varices, and to enroll patients in a screening program for hepatocellular carcinoma.