Considering the burden of HBV infection, complicated manner of HBV pathogenesis as reflected in natural history of HBV, social and economical status of most developing countries that harbor majority of HBV-infected patients, there is a need to update strategies to fight HBV infection in global perspective. This should consider the limitations of ongoing diagnostic approaches of HBV-related liver diseases. The real implications of serological markers should be reevaluated. It should also be remembered that initiation of antiviral therapy without proper patient counseling may be counterproductive. Finally, management strategy should be adjusted with the socio-economical conditions of developing countries. Also, serious consideration should be given to emergence of resistant strain of HBV due to antiviral therapy.