New standardized assays for the quantification of hepatitis B virus (HBV) DNA have yielded insights into the association of HBV DNA levels with the relative risk of developing liver disease. Quantification of HBV DNA has also played a role in the management of chronic hepatitis B by allowing criteria to be established for determining patient eligibility for antiviral therapy, monitoring response, and identifying the development of resistance. In addition to serum HBV DNA levels, the HBV genotype may influence disease progression and response to therapy. However, many of the studies that have included genotype assessment do not compare across the range of genotypes, and current management guidelines do not incorporate genotype determination. More recently, quantitative assays for intrahepatic HBV replicative intermediates, as well as hepatitis B e antigen and hepatitis B surface antigen, indicate that these factors may have promise in identifying patients likely to respond to treatment. Additional work is needed to standardize and validate these assays before they can be considered to be of true diagnostic value. A wide variety of research techniques are being used to investigate chronic hepatitis B. Further evaluation is needed to decide which will have the greatest clinical applicability.