The aim of this review is to examine the impact of hepatitis B virus (HBV) genotypes on biochemical and virologic response to antiviral drugs (alfa-interferon and pegylated-interferon alfa-2b, lamivudine, and adefovir dipivoxil) actually used for the treatment of chronic hepatitis, HBV related. International literature evidences that HBV genotypes D and C are associated with a lower rate of favorable response to alfa-interferon and pegylated-interferon alfa-2b therapy than genotypes A and B. The rate of resistance to lamivudine was higher in patients with genotype A infection than in patients infected by genotype D, whereas no difference in the risk of lamivudine resistance is found between patients with genotype B and patients with genotype C. In regard to the new nucleotide analogue, adefovir dipivoxil, a preliminary trial appears to provide no evidence of any difference in virologic response among the different HBV genotypes. The current study has determined that the different HBV genotypes have a very important impact on response to antiviral therapy, in particular interferon treatment. For this reason, determining the HBV genotype could be helpful for predicting the outcome of antiviral therapy in patients affected by chronic hepatitis B.