Since the registration of the first effective nucleoside analogue against the hepatitis B virus almost two decades ago, major progress has been made in the management of chronic hepatitis B infection. However, hepatitis B-related morbidity and mortality remain a major global health threat. This is partly due to the escalating costs and the decrease in compliance related to the need for prolonged therapy for most patients who cannot be "cured". New biomarkers such as quantitative hepatitis B surface antigen might help to determine if hepatitis B e antigen negative patients can be taken off nucleos(t)ide analogues. On the other hand, novel compounds that target the viral life cycle or modulate host immune response are in the pipeline. In the next few years, one should expect breakthrough advancement to be made leading to a "cure" for patients with chronic hepatitis B infection by inducing hepatitis surface antigen loss with or without the development of the hepatitis B surface antibody. In addition, attention and necessary actions should also be taken in patients with hepatitis B infection who are being treated with immunosuppressive therapy and direct anti-viral (DAAs) agents for hepatitis C infection to prevent hepatitis from hepatitis B reactivation.