Chronic hepatitis B virus (HBV) infection is a well-recognized risk factor for the development of hepatocellular carcinoma (HCC), which is becoming a more prevalent clinical problem, especially in HBV-endemic areas. It is estimated that 1.25 million people in the United States and more than 300 million people worldwide are chronically infected with HBV. Despite the introduction of universal vaccination against hepatitis B in over 100 countries, persistent HBV infection is still a serious problem worldwide, causing an estimated annual death rate of one million. It may take several decades until the effect of vaccination will be translated into reduced transmission and morbidity. Meanwhile, patients with persistent HBV infection require better antiviral therapeutic modalities than are currently available. It is well accepted that antiviral therapy for chronic hepatitis B is effective to improve prognosis of patients with HBV by preventing development of hepatitis state and HCC. The therapeutic endpoints for hepatitis B treatment are: 1) sustained suppression of HBV replication, as indicated by HBsAg and HBeAg loss, 2) decrease of serum HBV DNA of an undetectable level by a non-PCR method, 3) remission of disease, as shown by normalization of ALT, 4) improvement in liver histology, and 5) reduction of the acute exacerbation, cirrhosis, and HCC. In the present, the antiviral treatment of hepatitis B consists of either interferon alpha or oral lamivudine alone or in combination with existing therapy. Each major antiviral drug of interferon alpha and lamivudine has pros and cons, and effect of combination therapy of both drugs is also still limited. More powerful and safe new antiviral therapies are required to achieve final goal of these therapeutic endpoints. Management of chronic hepatitis B requires significant knowledge of approved pharmacotherapeutic agents and their limitations. Therapeutic options for managing hepatitis infection after liver transplantation (LT) are also evolving. In this article, we would like to adjust the focus of current clinical issue of antiviral therapy for hepatitis B and also indicate the issue of LT for patients with hepatitis B.