Two billion people of the world have been infected with the HBV at some point of their life. About 350–400 million people are chronically infected with the HBV and it seems that they would harbor HBV for the rest of their life. About 20% chronic HBV carriers are prone to develop severe complications like liver cirrhosis, hepatic decompensation and HCC. Patients with chronic HBV infection can show acute flare or reactivation of hepatitis either spontaneously or due to use of anticancer or antiviral drugs. Also, coinfection with other hepatitis viruses or hepatotoxic agents may cause liver failure. Thus, it is a difficult to fix a strategy for management of these patients. Several recommendations are available from different professional liver organization regarding management of chronic HBV infection. However, most of the patients in developing countries may not be treated according to these recommendations due to social, technical and economical problems. In this context, a major concern about treatment of chronic HBV infection is related to personalize the therapeutic approach. In complete therapy may cause emergence of resistant HBV. A comprehensive discussion about this has been made which is essential in clinical set up.