Viral hepatitis is a major cause of chronic liver disease, liver failure, and hepatocellular carcinoma worldwide, resulting in significant morbidity and mortality. New insights into the pathogenesis and molecular biology of hepatitis viruses have led to the discovery of novel antiviral agents. Likewise, a greater understanding of the natural history of chronic infection, predictors of disease progression, and predictors of virologic response to therapy has resulted in more effective treatment strategies. Recent data have increasingly demonstrated that the ability to achieve a successful response to antiviral therapy may significantly reduce the risk of progressive liver disease and hepatocellular carcinoma. Immunization practices and the use of potent antiviral therapy may have a major impact in reducing the burden of chronic liver disease and the incidence of hepatocellular carcinoma associated with chronic hepatitis B and chronic hepatitis D. Individualized treatment strategies and the development of direct acting antiviral agents may lead to further improvements in the ability to achieve a sustained virologic response to therapy in chronic hepatitis C. With new advances in the treatment of chronic hepatitis, efforts to optimize viral suppression while reducing the potential for antiviral drug resistance will become increasingly important.