Chronic hepatitis B is one of the world's most common serious diseases with > 300 million patients worldwide. Currently recommended treatments include conventional interferon (IFN), lamivudine and adefovir. Recently, peginterferon-alpha2a (PEG-IFN-alpha2a, Pegasys; Hoffmann-La Roche & Co.) has been approved for use in patients with chronic hepatitis B in the US, the EU, Switzerland, Turkey and in several countries in the Asia-Pacific region. Several trials have been carried out using PEG-IFN-alpha2a (40 kDa) compared with conventional IFN, lamivudine monotherapy and a combination of PEG-IFN-alpha2a and lamivudine in patients with hepatitis Be antigen- (HBeAg) positive chronic hepatitis B, and patients with HBeAg-negative chronic hepatitis B. PEG-IFN-alpha2a was shown to be superior to conventional IFN in HBeAg-positive disease and to lamivudine in both HBeAg-positive and HBeAg-negative chronic hepatitis B. Although there was greater suppression of virus while on therapy, the combination of lamivudine and PEG-IFN-alpha2a did not enhance sustained response at the end of the 24-week follow-up period, compared with PEG-IFN monotherapy. In addition, approximately 3% of patients underwent hepatitis B surface antigen (HBsAg) seroconversion - the ultimate marker of therapeutic response, which is rarely seen following treatment with antiviral agents. The side effect profile was reasonable. PEG-IFN-alpha2a could become the treatment of choice in many patients with both HBeAg-positive and HBeAg-negative disease and, in those who fail to respond, consideration could then be given to the use of antiviral agents.