Serologic assays for HBV are the mainstay diagnostic tools for HBV infection. However, the advent of molecular biology-based techniques has added a new dimension to the diagnosis and treatment of patients with chronic HBV infection. Over the past decade, improvements in molecular technology, permitting detection of as few as 10 copies/mL of HBV DNA in serum have led to redefinitions of chronic HBV infection, as well as thresholds for antiviral treatment. As the sensitivity of these molecular techniques continues to improve, the challenge will be to standardize these as-says as well as define clinically significant levels of HBV replication.