Approximately 400 million individuals worldwide have developed chronic hepatitis B after exposure to the hepatitis B virus (HBV). Up to 40% of these will eventually develop serious hepatic complications. Although widespread immunization, improved blood supply testing, and emphasis on safe sex have significantly decreased new HBV infections, the large reservoir of infected individuals (400 million) remains a serious health problem. At present, only two agents are available for the treatment of chronic hepatitis B: interferon alfa and lamivudine. Both are associated with important limitations of efficacy or safety, or both. These limitations and other problems associated with the evaluation of current and investigational therapies for chronic hepatitis B give rise to several key issues in management of HBV: duration of therapy, goals of therapy, need for standardization of the measurement of clinical responses, and definitions of response to therapy. The last two of these key issues are of particular concern. The lack of similarity in study designs, the use of inconsistent definitions of and criteria for therapeutic response, and the lack of uniformity in assays to detect HBV DNA titers hamper consistent evaluations of treatment. Therefore, there is a need for the scientific community to standardize the measures of performance and methods of analysis and reporting of clinical trials for current and new drugs.