As a leading cause of liver cirrhosis and hepatocellular carcinoma, chronic hepatitis B poses a major health care problem. Currently approved therapeutic options include interferon-alpha, pegylated interferon-alpha, lamivudine and adefovir. Interferon-alpha can induce long-term suppression of viral replication in a proportion of patients. However, treatment is associated with considerable side effects. Lamivudine and adefovir effectively suppress viral replication and induce histological improvement in the majority of patients. However, recurrence rates are high after cessation of treatment. During long-term treatment about 20% lamivudine-resistant mutants emerge annually, while currently available studies suggest that this number is about 3% for adefovir after two years of therapy. Efficacy of the respective antivirals is affected by virological and clinical parameters, thus requiring individual treatment strategies.