More than two billion people have been infected with Hepatitis B virus (HBV) worldwide, and more than 350 million suffer from chronic HBV infection. Chronic hepatitis B can lead to serious complications such as cirrhosis and hepatocellular carcinoma (HCC). HBV is the hepadnaviridae with an incomplete double-stranded DNA genome of 3.2 kb. HBV genome contains four overlapping open reading frames that encode the surface, core, X, and polymerase proteins. Applications of molecular biology in the diagnosis and management of patients with chronic hepatitis B virus infection include: plasma HBV DNA viral load, genotypes, the mutants in Enh II/ BCP/ PC region and the PreS region, and drug-resistance mutations in P gene. High HBV load ( 10 exponent 4 copies/mL) is independ ently associated with the occurrence and post treatment recurrence of HCC, HBV genotype (CB) is associated with increased risks of cirrhosis and HCC. Different genotypes have distint patterns of mutations. The mutants in Enh II/ BCP/ PC region and the PreS region are sig nificantly associated with the increased risks of cirrhosis and HCC. HBV DNA load, HBV genotypes, and the mutations in Enh II/ BCP/ PC region and the PreS region can be used for the prediction of HCC. Early detection of drug-resistance mutations in gene P is very important for explaining treatment failures and guiding subsequent treatment decisions. Some molecular markers have the potential diagnosis and management of patients with chronic hepatitis B virus infection in the future include: total HBV DNA and cccDNA load in liver or cccDNA level in plasma.