The global health challenge posed by the hepatitis B virus (HBV) centres around the widespread distribution and the serious complications as a result of persistent infection with the virus. As with other chronic diseases mediated by pathogens such as human immunodeficiency virus (HIV) and hepatitis C virus (HCV), clinicians are searching for epidemiological, pathological and viral characteristics of HBV infection that may lead to more effective management of patients with chronic infection. Unlike HCV, the role of HBV genotype in disease progression, severity, response to therapy and drug resistance is still under investigation and just beginning to be clarified. This review examines the potential role of HBV genotype determination in the clinic with emphasis on how this genetic information may used to provide effective management for the treatment of patients with chronic hepatitis B.