In recent years, marked progress has been made in the treatment of chronic hepatitis B. Several agents have been approved: interferon alpha-(IFN), pegylated interferon alpha2a (PEG-IFN alpha2a), lamivudine, adefovir, entecavir, telbivudine and recently, tenofovir. Each drug has advantages and limitations. IFN and PEG-IFN alpha2a have the advantage of inducing a sustained virologic response after a defined, limited course of treatment. However, these drugs are only effective in a minority of patients and have frequent side effects. Analogues have the advantage of being administered orally, with good safety profiles and a potent antiviral effect. However, these drugs need to be administered indefinitely since withdrawal of therapy is generally associated with reactivation, and a sustained response is uncommon except in HBeAg positive patients who develop HBe seroconversion. In case of HBe seroconversion, therapy should usually be continued for at least another 24 weeks. The efficacy of lamivudine is limited by the emergence of lamivudine-resistant HBV. Adefovir is associated with a moderate incidence of resistance but its antiviral effect is not optimal. Entecavir has shown to be more effective with a favourable safety profile and a low incidence of resistance. Telbivudine is more potent and has a lower rate of resistance than lamivudine but the resistance rate is significantly higher than other approved drugs. Tenofovir has a potent antiviral effect with a good resistance profile.