Chronic hepatitis B is a world-wide health problem and now at least 250 million people have been infected with hepatitis B virus. Current treatment of hepatitis B rarely achieves a cure because the viral replication template which called covalently closed circular DNA (cccDNA) are resistant to conventional therapies. The phenotype and function of natural killer cells from chronic hepatitis B patients are different to those from acute hepatitis B patients, suggesting that the function of NK cells may be related to clearance of HBV. Some studies have suggested that the differentiation, development and activation of natural killer cells are controlled by the mammalian target of rapamycin. The present review will mainly focus on the biology of hepatitis B virus, the differentiation and development of natural killer cells, and the progress of metabolism of natural killer cells. DOI: 10.11855/j.issn.0577-7402.2017.07.16