The ideal goal of chronic hepatitis B(CHB) treatment should be suppression of emergence of hepatocellular carcinoma through the disappearance of hepatitis B s antigen(HBs Ag) rather than the control of serum hepatitis B virus-DNA level. For this purpose, various types of combination therapies using nucleoside analogs(NAs) and interferon(IFN) have been conducted. The therapeutic effects of combination of two different kinds of agents are better than those of the monotherapy using NAs or IFN alone, probably because different pharmaceutical properties might act in a coordinated manner. Recently, combination therapies with NAs and IFN and sequential therapies with NAs administration followed by IFN therapy have been routinely employed. We previously reported that combination therapy using entecavir(ETV) and pegylated(PEG)-IFN showed antiviral effects in 71% of CHB patients; the effect of this combination was better than that using lamivudine(LAM) and PEG-IFN. This is partially explained by the better antiviral effects of ETV than those of LAM. In our analysis, the cohort of CHB consisted of the patients who showed a flare-up of hepatitis before antiviral therapy, and their baseline HBs Ag levels were relatively low. Therefore, in addition to the combination of the agents, the appropriate selection of patients is critical to achieve a good viral response. The ideal goal of chronic hepatitis B (CHB) treatment should be suppression of hepatocellular carcinoma through the disappearance of hepatitis B s antigen (HBs Ag) rather than the control of serum hepatitis B virus-DNA level. For this purpose, various types of combination therapies using nucleoside analogs (NAs) and interferon (IFN) have been conducted. The therapeutic effects of combination of two different kinds of agents are better than those of the monotherapy using NAs or IFN alone, probably because of different pharmaceutical properties might act in a previously described combination therapy using entecavir (ETV) and pegylated (PEG) -IFN showed antiviral effects in 71 % of CHB patients; the effect of this combination was better than that using lamivudine (LAM) and PEG-IFN. This is partially explained by the better antiviral effects of ETV than those of LAM. In our analysis, the cohort of CHB consisted of the patients who showed a flare-up of hepatitis before antiviral therapy, and their baseline HBs Ag levels were relatively low. Thus, in addition to the combination of the agents, the appropriate selection of patients is critical to achieve a good viral response.