The chronic infection of hepatitis B virus (HBV) inflicts 250 million people worldwide representing a major public health threat. A significant sub-population of chronically infected HBV patients eventually develop cirrhosis and hepatocellular carcinoma (HCC) which aggravate the issues caused by hepatitis alone. Unfortunately, none of the current standard therapies for chronic Hepatitis B (CHB) result in a satisfactory clinical cure rate. Driven by a highly unmet medical need for novel and more effective treatments of HBV infection, multiple pharmaceutical companies and research institutions have been engaged in drug discovery and development to improve the CHB functional cure rate, which is defined by sustainable viral suppression and HBsAg clearance after a finite treatment. This review summarizes the recent significant advances in the discovery and development of novel small molecule anti-HBV compounds, highlighted by representative structures, mechanism of action (MoA), and biological activities. Lastly, it is believed that improved CHB functional cure rate may be accomplished via the combination of molecules with distinct MoAs. Thus some of the molecules may evolve into key components of a suitable combination therapy leading to superior outcome of clinical efficacy in the future.