Currently, there are several antiviral treatments effective for suppression of viral replication but still failed to cure HBV infection in patients with chronic hepatitis B. The short-term treatment goals are thus to control hepatitis activity, to obtain hepatitis B e antigen (HBeAg) seroconversion, and to improve necroinflammatory activity and fibrosis of the liver. Six drugs have been worldwide approved for the treatment of chronic hepatitis B at present: conventional IFN (IFN) alfa, lamivudine (LAM), adefovir dipivoxil (ADV), pegylated IFN (Peg-IFN) alfa, entecavir (ETV) and recently telbivudine (LdT). Conventional IFN alfa monotherapy has a narrow range of efficacy, is associated with several adverse effects and is inconvenient because of frequent injections. Lamivudine is better tolerated; but virologic response to lamivudine is frequently not durable and prolonged lamivudine treatment is commonly associated with the emergence of drug-resistant HBV mutants. Adefovir dipivoxil is effective and has been approved for the treatment of chronic hepatitis B in many countries, but is nephrotoxic at doses higher than 10 mg per day for long time. Pegylated IFN alfa has been shown to be superior to conventional IFN alfa and lamivudine, and has already been approved for the treatment of chronic hepatitis B. Overall, satisfactory virologic and serologic responses could be achieved using pegylated IFN alfa alone in around 30-44% of these patients. Entecavir, a carbocyclic deoxyguanosine analog, which is active against both lamivudine- and adefovir dipivoxil-naïve and -resistant HBV, is the most potent anti-HBV agent ever discovered. In addition, the 4-year drug resistance rate is <1.0% in selected lamivudine-naïve patients. LdT is another thymidine nucleoside analogue with potent in vitro activity against HBV and approved for CHB. Recent phase III GLOBE trials have proved this agent to be more effective in the treatment of HBeAg+ve and -ve chronic hepatitis B than lamivudine. However, resistance to telbivudine was noted in around 10% of subjects after 104-week continuous therapy, although still fewer than that in patients receiving lamivudine.