Over 240 million people worldwide are chronically infected with hepatitis B virus (HBV) although the HBV prophylactic vaccine has dramatically reduced new infections. However, still up to 680000 deaths per year are caused by HBV-related end-stage liver diseases and liver cancer. Currently, strategies for the treatment of Chronic Hepatitis B (CHB) include interferon-alpha (IFNα) and nucleos(t)ide analogues (NAs), but it is difficult to achieve the ideal clinical treatment endpoint, namely hepatitis B surface antigen (HBsAg) negative or serological conversion. Many teams are trying to develop more effective treatments, targeting key steps in the HBV life cycle and potential host factors, aiming to great medical needs for CHB patients that have not yet been met. This article reviews the advances in the research and development of the potential drugs in clinical development and partial preclinical stages.