Chronic hepatitis B virus (HBV) infection is a serious clinical problem because of its worldwide distribution and possible adverse sequelae. It is particularly important in the Asia–Pacific region where HBV infection is highly prevalent and usually acquired perinatally or in early childhood. It is now known that chronic HBV infection is a dynamic interaction between virus, hepatocyte and the host’s immune response. The natural history of chronic HBV infection can be divided into three phases: high replicative or viraemic ‘immune tolerance phase’ followed by ‘immune clearance phase’ and then the low replication ‘residual phase’. The clinical course of chronic HBV infection is characterized by a series of exacerbations and remissions during the ‘immune clearance phase’, which may lead to hepatic decompensation, progression of liver disease, development of cirrhosis and hepatocellular carcinoma (HCC). It is of paramount importance to arrest HBV replication as early as possible to reduce infectivity, improve hepatic injuries, prevent progression to cirrhosis or HCC and thereby prolong survival. There are many potentially effective agents with different mechanisms of action and there is substantial accumulated experience with these therapies, but there is also still a need for practical recommendations such as: (i) who should be treated; (ii) when to treat such patients; (iii) which drug(s) or strategy would be most cost-effective for the patient under consideration; (iv) how the patient should be monitored; (v) what benefit the patient can expect from such treatments; (vi) what can be done for special groups of patients, such as decompensated cirrhosis immunocompromised patients or children; and (vii) what treatment of chronic HBV infection could be expected in the 21st century. The Asia–Pacific region not only has the greatest number of patients with chronic HBV infection, but also has conducted important clinical trials. It is relevant and mandatory to coordinate all current knowledge to reach a consensus and to make guidelines for the treatment of chronic HBV infection in this region.