New optimism surrounds treatments for chronic hepatitis B (CHB). Interferon- alpha , lamivudine, and adefovir dipivoxil are currently approved by the United States Food and Drug Administration for the treatment of CHB. All 3 treatments possess unique characteristics with respect to their side effect profiles, potencies, and treatment niches within the spectrum of CHB. New agents, which are in various stages of clinical development, represent potential improvements within existing, as well as novel, classes of antiviral therapy, and they offer significant promise of a cure for the many patients with chronic and progressive hepatitis B. However, there remain many challenges in understanding the implications of drug resistance, the role of combination therapy, and how to define the response to therapy within subsets of patients with hepatitis B.