Abstract: Chronic hepatitis B virus (HBV) infection is a serious health issue in the Asia-Pacific region, where most infections are acquired perinatally or during early childhood and may lead to the development of chronic sequelae such as liver cirrhosis and hepatocellular carcinoma (HCC). Studies have identified several host factors (age, gender, immune status) and viral factors (HBV viral load, genotype, basal core promoter and other naturally occurring HBV mutations) associated with disease progression. Other factors, including lifestyle (habitual alcohol consumption, cigarette smoking), exposure to aflatoxin, and viral superinfection may also influence liver disease progression in patients with chronic HBV. This review highlights pertinent data on the factors associated with progressive HBV-related liver disease in patients with chronic hepatitis B. An enhanced understanding of factors associated with HBV disease progression may lead to improvements in the selection of candidates for intervention and overall disease management. Interventions such as lifestyle changes and antiviral therapy may thus prevent or reduce disease progression.