The aims of antiviral therapy for chronic hepatitis B are to sustain suppression of hepatitis B virus (HBV) replication and to achieve remission of liver disease activity. Currently, interferon- and lamivudine have been approved by the FDA for the treatment of chronic hepatitis B. However, the efficacy of interferon- is limited to a small percentage of patients, and many adverse effects of the treatment exist. A major drawback of continued lamivudine therapy is the high incidence of drug-resistant mutant. Several antiviral drugs such as adefovir dipivoxil, entecavir, clevudine, and emtricitabine are under clinical investigation as the potential agents for mono- or combination therapy, which have been shown to be highly effective for chronic hepatitis B. Especially, some of them have a strong antiviral effect against lamivudine-resistant mutant as well as wild-type HBV. Long-term treatment with adefovir dipivoxil does not lead to the emergence of resistant virus. Combination therapy seems to represent the future treatment for chronic hepatitis B because of its antiviral synergistic effect and minimal incidence of drug-resistant mutant, but the choice of agents for combination therapy needs further study.