Chronic viral hepatitis has emerged as one of the most common causes of disease and death worldwide. Because of their unique modes of replication and intimate association with the host immune system, hepatitis B virus (HBV) and hepatitis C virus (HCV) pose challenging problems to scientists in basic and applied research as well as to clinicians engaged in disease management. Although approved antiviral therapy is available for chronic HBV, the emergence of viral resistance provides a rationale for the development of novel chemotherapeutic agents. The lack of a robust cell culture system for HCV replication and a readily accessible small-animal model of HCV infection have hampered the development of antiviral agents for HCV. Neverthe-less, new antiviral agents targeting HCV are now in preclinical and clinical development.