Interferon-alpha is currently the only therapy approved for treatment of chronic HBV in the United States and Europe. Interferon-alpha therapy causes loss of HBeAg and HBV DNA in approximately a third of treated patients, and the loss of these markers of active viral replication is associated with improvements in hepatic histology and ALT levels. However, the long-term effects of interferon-alpha on morbidity and mortality, and especially on the incidence of the complications of chronic HBV infection, remain to be defined. The currently available treatment for chronic HBV is far from perfect. Interferon therapy is usually associated with significant side effects and requires subcutaneous administration. Additionally, there are a large number of patients who either fail to meet criteria for treatment, or who, with therapy, fail to respond (at least 60% of all patients). Moreover, interferon treatment is expensive (approximately $5,000 for a 16 week course of 5MU daily). Hence the search continues for effective, orally-available and cost-efficacious therapy. Of the agents available, the nucleoside analogues appear to have the greatest promise. The availability of cell culture systems and animal models for studying potential anti-HBV drugs will aid in the future development of these agents. Therapeutic vaccines, and combination therapies (given either concurrently or sequentially) may also play a future role in the management of chronic HBV infection. While prevention of disease must be a primary goal in the war against this common infection, a continued focus must be maintained on the treatment of the approximately 300 million individuals world-wide with established chronic HBV infection.