Chronic hepatitis B virus (HBV) infection is a key factor in the progression of liver disease and can lead to liver insufficiency, cirrhosis and hepatocellular carcinoma (HCC). The main goal of treatment is to inhibit or eliminate HBV replication and reduce hepatitis activity, thereby reducing or slowing the progression of liver disease. Nucleoside (acid) analogs may lead to rapid inhibition of HBV replication, normalization of serum transaminases, and restoration of liver function, thereby improving the survival cycle of patients with hepatic decompensation. Long-term nucleoside (acid) analogue therapy may improve liver histology, reverse liver fibrosis, and reduce disease progression, such as liver cancer. Limited cycles of interferon (IFN)-α therapy may provide long-term benefits, including sustained and cumulative virologic responses, as well as hepatitis B surface antigen (HbsAg) serum clearance and reduced development of cirrhosis and/or hepatocellular carcinoma. PEGylated interferon (PEG-IFN) and newer Nucs drugs may achieve better long-term outcomes because of their improved efficacy and lower risk of resistance development.