In clinical treatment, loss of serum hepatitis B virus e antigen (HBeAg) and appearance of anti-HBe ( HBeAg seroconversion ) is one of the important criteria for therapeutic efficacy of chronic hepatitis B. Herein, the history of discovery of HBeAg, and the biological and medical implication of this hepatitis B virus (HBV) encoded protein are presented. In addition, the immunogenicity of HBeAg and core antigen (HBcAg) is compared, and the immunological basis as well as the importance of HBeAg seroconversion is analysed.