Measurement of conventional markers has provided a general understanding of HBV infection, and conceptual advances in knowledge of the clinical and serologic events associated with persistent HBV infection have resulted from the development and application of new methodologies. These studies suggest that persistent HBV infection is a dynamic process, with replicative and nonreplicative phases, that nonreplicative infection may be the precursor of PHC, and that the natural history of persistent infection can be modified by a variety of factors, including viral reactivation and viral superinfections. Further understanding of these phenomena may lead to the development of new therapeutic approaches.