Worldwide, chronic hepatitis B virus infection is a major cause of end-stage liver disease and hepatocellular carcinoma. While the past two decades have brought major advances in the availability of treatments to help delay or prevent these outcomes, treatment of chronic hepatitis B remains a serious challenge. With the recent availability of potent new nucleot(s)ide such as entecavir, tenofovir and telbuvidine, I still use pegylated interferon (PEG-IFN)-α for the treatment of chronic HBeAg-positive patients. This is based on its relatively higher effectiveness in restoring the host immune control on viral replication, resulting in sustained diseases remission in a proportion of patients, a finite course of therapy and the absence of viral resistance. The two major hindrances to its wide application are its lack of effectiveness in a large proportion of patients and its side-effect profile. The former shortcoming can be circumvented to a certain extent with the use of response predictor models. Recently, based on long-term follow-up study, the better durability of sustained response further enhances the confidence in the use of PEG-IFN-α in chronic HBeAg-positive patients.