Chronic hepatitis B infection affects >300 million people worldwide and is a leading cause of liver failure and cancer. Current approaches to treatment for chronic hepatitis B involve suppression of hepatitis B virus (HBV) DNA with the use of nucleoside analogues. Chronic suppressive therapy rarely results in a “functional cure” or absence of detectable HBV DNA in plasma and loss of detectable hepatitis B surface antigen after cessation of therapy. The major obstacles to achieving a functional cure are the presence of covalently closed circular DNA and ineffective/exhaustive immune system. This presentation focuses on novel approaches to target viral life cycle and host immunity to achieve a functional cure.