Infection with hepatitis B and/or hepatitis C virus is strongly associated with hepatocellular carcinoma (HCC). HCC likely develops through a sequence of chronic inflammation to fibrosis to cirrhosis and, eventually, dysplasia. Medical therapies aimed at the prevention of HCC are predicated on the interruption of this sequence by means of antiviral therapy. In this review, the authors summarize the available experience with prophylactic medical therapies and a number of questions that remain unanswered. Overall, although it appears that interferon-alpha therapy is beneficial in the prevention of HCC in patients with viral hepatitis, more experience is required before definitive recommendations can be made.