Currently approved treatment of patients with chronic hepatitis B infection is insufficient to achieve functional cure. Numerous new compounds are identified, and among many, capsid assembly modulators (CAMs) and nucleic acid polymers (NAPs) are 2 classes of virus-directing agents in clinical development. CAMs interfere with viral pregenomic RNA encapsidation and are effective in viral load reduction but have limited effects on hepatitis B surface antigen (HBsAg). NAPs prevent HBsAg release from hepatocytes and induce intracellular degradation, leading to potent suppression of serum HBsAg when combined with nucleoside analogues and pegylated interferon demonstrated by initial data, but awaiting further confirmation studies.