One of the major concerns in clinical hepatology is related to HBV mutants. Mutant HBV is difficult to diagnosis in most developing countries. It is a problem to explore its significance in disease pathogenesis. Containment of mutant HBV constitutes another major challenge in the context of management of HBV. Some of these mutants may originate spontaneously or mutants HBV may be induced by vaccine or antiviral drugs in HBV-infected subjects. The differences of HBV mutants should be completely understood to develop effective strategies for their containment. A comprehensive description of precore/core promoter mutants have been given in this chapter. Also, clinical significance of HBeAg-negative chronic hepatitis B patients has been described along with the mechanism of their genesis. Vaccine-induced mutants and drug-induced mutants have also been described with recent data from eminent laboratories. Finally, the effects of these mutants on diagnostic assays have been described. Taken together, almost all aspects of HBV mutants have been described comprehensively so that the information may be properly used for better management of HBV-infected subjects in clinics.