Hepatitis B virus (HBV) infection is a major global health challenge. HBV can cause significant morbidity and mortality by establishing acute and chronic hepatitis. Approximately 250 million people worldwide are chronically infected, and more than 2 billion people have been exposed to HBV. Since the discovery of HBV, the advances in our understanding of HBV virology and immunology have translated into effective vaccines and therapies for HBV infection. Although current therapies successfully suppress viral replication but rarely succeed in viral eradication, recent discoveries in HBV virology and immunology provide exciting rationales for novel treatment strategies aiming at HBV cure.