Approximately 350-420 million people worldwide are chronically infected with hepatitis B virus (HBV). Chronic hepatitis B can result in liver cirrhosis, hepatic decompensation, and hepatocellular carcinoma. Reactivation of hepatitis B is possible in patients with inactive or resolved hepatitis B often leading to liver failure. Those sequelae may be prevented by effective antiviral therapy. Interferon alfa, pegylated interferon alfa and five direct antiviral nucleoside and nucleotide analogues are approved for the treatment of chronic hepatitis B. Still, whom to treat, which therapy regimen to use, and when to begin treatment remain the challenges in the management HBV-infected patients. This review focuses on the current treatment concepts for chronic hepatitis B.