The treatment of chronic hepatitis B is now based on the using of pegylated interferon or nucleoside or nucleotide analogs. In the majority of cases, these drugs can control viral replication with an hepatitis B virus (HBV) DNA negativation after approximately 6 months of therapy. In case of primary non response, it is necessary to modify antiviral therapy and if resistance appears to combine a nucleoside and a nucleotide analog. In patients treated by nucleoside analog, if HBV DNA is not negative or do not dramatically decreases at the week 24, it is also necessary to add a nucleotide analog. However, for adefovir therapy, it is usually preferable to wait at week 48. In summary, a regular following every 3 months of HBV DNA detection by a sensitive method (Real Time PCR) allows to evaluate the therapeutic efficacy and to prevent the risk of biochemical and clinical rebound due to appearance of resistance mutations.