Three drugs are currently available for the treatment of chronichepatitis B: interferon-alpha, lamivudine and adefovir dipivoxil. Standard interferon-alpha induces a sustained response in only a minority of patients (10-30 %) and is associated with a poor tolerability which limits duration of therapy. The nucleoside (lamivudine) and nucleotide (adefovir dipivoxil) analogs have the advantages of oral administration and excellent tolerance. Lamivudine, administered for 12 months, induces a sustained response in approximately 20 % of the HbeAg positive and in 5 % of the HBeAg-negative patients. Long-term therapy increases the rate of sustained response but is impaired by a high rate of resistance (50 % at 3 years). Adefovir dipivoxil, administered for 12 months, induces a sustained response in 12 % of HBeAg-positive patients. Adefovir has a similar antiviral efficacy in HBeAg-negative patients. The incidence of resistance to adefovir is low (6 % at 3 years). Thus, the currently available drugs have a limited effectiveness and new more powerful drugs or new therapeutic strategies are necessary. Recent studies showed that the efficacy of pegylated interferon was higher than the standard interferon. Evaluated therapeutic combinations, pegylated interferon and lamivudine on the one hand and to adefovir and lamivudine on the other hand, did not show superiority as compared to the monotherapy by pegylated interferon and to adefovir, respectively. A number of nucleoside analogs, with favorable toxicity profiles and a promise of increased effectiveness against HBV, are at various stages of clinical development. Results of phase III trials of entecavir confirmed its efficacy and safety leading to registration in the next future. Emtricitabine does not seem more effective than lamivudine. The results of phase II studies of telbivudine and clevudine are promising. However, one may expect that their use in monotherapy could not induce a high rate of sustained response and that long-term therapy or combination should be needed to improve efficacy and/or reduce resistance.