Prior to the introduction of viral inactivation techniques in the mid-1980s, the vast majority of patients with hemophilia who received plasma-derived clotting factor concentrates were exposed to and infected with the hepatitis C virus (HCV), a lipid-enveloped bloodborne pathogen. Hemophilia patients may also have been co-infected with the human immunodeficiency virus (HIV) after receiving contaminated blood products. HCV mono-infection has a very slow progression, but patients with hemophilia who are co-infected with HCV and HIV can exhibit a comparatively rapid progression of liver disease. Potential complications of chronic HCV infection are subsequent cirrhosis with hepatic failure and the ultimate onset of hepatocellular carcinoma. The treatment of either of these may involve orthotopic liver transplantation. Liver biopsy and morphologic evaluation of tissue remain the current "gold standard" by which the severity of HCV-induced liver disease can be reliably assessed. Although there has been a reluctance to perform invasive percutaneous liver biopsies in patients with hemophilia, available evidence suggests that they appear to be safe and they certainly provide greater specificity and sensitivity than radiographic techniques such as computerized tomography or magnetic resonance imaging. Treatment of HCV-infected patients is targeted towards preventing the progression of early cirrhosis and end-stage liver disease. The current standard of care for individuals with hemophilia has generally been considered to be the combination of standard interferon-alpha (IFN-alpha) with ribavirin for at least 6 months. Data concerning the use of PEGylated IFN, substituting for standard IFN-alpha, are now emerging, although relatively little of this information relates specifically to hemophilia patients with liver disease. Nevertheless, the favorable data from large non-hemophilia-related HCV disease with early cirrhosis have been extrapolated to the hemophilia scenario, and there has been no evidence in the limited number of hemophiliacs treated in this way to refute this conclusion.