Hepatitis B virus (HBV) infection affects about 300 million people worldwide. Although antiviral therapies have improved the long-term outcomes, patients often require life-long treatment and there is no cure for HBV infection. New technologies can help us learn more about the pathogenesis of HBV infection and develop therapeutic agents to reduce its burden. We review recent advances in development of directing-acting antiviral and host-targeting agents, some of which have entered clinical trials.