Chronic hepatitis B virus (HBV) infection has a variable course leading to cirrhosis and hepatocellular carcinoma (HCC). The pathogenesis and clinical outcome of HBV infection are strictly dependent on both viral factors, such as life cycle and genotypic variants, and host immune response (i.e. viral persistence). Although therapy of hepatitis B is evolving, which between single and/or combined agents are most effective, how long therapy should last, which criteria should be used to start or continue and switch or stop therapy are to be defined. Two major groups of therapies are currently utilized for chronic hepatitis: immunomodulatory (interferons) and antivirals (nucleoside and nucleotide analogues), all with their own advantages and limitations. In fact, the development of specific antiviral therapies has provoked the appearance of a relevant problem: drug resistances. The emerged antiviral drug-resistant strains of HBV leads to a poor prognosis for infected patients. Thus, many basic and clinical research challenges remain in defining optimal means of management of viral hepatitis B and its related liver diseases. This paper provides a review of new available and developing treatment options for HBV associated liver diseases. In the near future the most realistic therapeutic option for the majority of patients with HBV infection will be combination and/or long-term use of new and stronger antiviral drugs, if they maintain good safety profiles, achieve low resistance rates and will be available at lower prices.