The causal agent for hepatitis B is called hepatitis B virus (HBV). It is a partially double stranded circular DNA virus of the family Hepadnaviridae. It has been implicated as the leading cause of hepatocellular carcinoma and only second to tobacco among the global human carcinogens. Liver damage as a result of HBV infection is due to host immune response and is modulate by cytokines. The HBV is classified into 10 genotype denoted as A, B, C, D, E, F, G, H, I and J together with several sub-genotypes which have diverse geographical distribution. These genotypes influence liver disease progression and severity as well as response to antiviral therapies. Mutations in the S-gene have been implicated in the paradoxical coexistence of HBsAg and the anti-HBs antibodies which is associated with advanced liver diseases including hepatocellular carcinoma and liver cirrhosis. Management of HBV is by using antiviral therapy but there is no treatment that can cure HBV. Therefore the practical alternative is vaccination but this is genotype specific. It therefore absolutely necessary to match vaccine strains with field strains. Success on this subject is contingent upon accurate diagnosis and routine genotyping. The concept paper also explicates the need for more elucidation of cytokine profiles in HBV virus infection since liver disease progression is cytokine modulated especially in the scenario where mutations are common yet they influence cytokine profiles.