The hepatitis B virus, as is the case of the hepatitis C virus, can be categorized in several genotypes. The genotyping of HBV is based on the nucleotide sequence divergence encoding the amino acids constituting the HBV surface proteins. Since the genotype of the hepatitis C virus is shown to be related to epidemiology and response to interferon therapy, one wonders whether this also holds for the hepatitis B virus. HBV genotypes clearly are found to be different in various geographical areas of infection. In Europe, genotypes A and D are predominant, whereas in Asian patients genotypes B and C are more frequent, and in the Middle-East the genotype D. Data concerning the clinical relevance are less clear but it seems that in Europe, the genotype A has a higher HBeAg clearance rate and a better outcome. In Asia, genotype B (and especially the genotype Bj) is associated with a higher HBeAg clearance and with less development of cirrhosis and HCC. The impact on spontaneous or therapy induced viral resolution is not yet clearly identified. Further evaluation in different countries is needed to delineate the impact of the genotype relative to other factors such as age at infection, level of serum transaminases and viral load, on the course of infection, complication, outcome of treatment and prognosis.