A global expansion of Hepatitis B virus (HBV) infection continues still now, and it poses a still big problem. Since the Australia antigen was discovered, HBV research has been continued by various methods, such as clinical medicine and epidemiology. However, the simple and efficient infection experimental systems (in vitro and in vivo) have not been established, because the host range of HBV is narrow. Therefore, the techniques of reverse genetics have contributed to HBV research greatly. We have established the HBV clones of various genotypes from the chronic hepatitis B patients, and have analyzed using the techniques of reverse genetics. Based on our results, it has become clear gradually how HBV pathogenesis related to the genotypes. In this paper, we would like to introduce the outline of research analyzed by reverse genetics about HBV.