With the discovery of genotypes of HBV, it is now required to assess epidemiology, pathogenesis, and therapy of HBV infection from a new angle. HBV genotypes have provided possible solution to several unresolved aspects about HBV epidemiology and pathogenesis. At the same time, several confusions have surfaced with the advent of HBV genotypes. Several alterations have been adopted in HBV study on the basis of HBV genotypes. The clinical significance of HBV genotypes have also been shown by several studies. It seems that some of the HBV genotypes are prone to induce hepatocarcinogenesis and severe liver damages, whereas, others are less virulent in this context. However, question remains when asymptomatic HBV carriers are found in high percentage in all genotypes. In addition, the concept of genesis of HBV genotype is not so clear to most physicians or to hepatologists. Simple and comprehensive description HBV genotypes have been provided in this chapter so that the clinical significance of HBV genotypes is well understood by physicians of all levels. The authors have also provided description about significance about HBV genotype during antiviral therapy in patients with chronic hepatitis B.