The treatment goal for chronic hepatitis B is true eradication of the hepatitis B virus, but this is rarely achieved with first-line treatment regimens because of an inability to disrupt covalently closed circular DNA and an inadequate host immune response. Therefore, new antiviral agents are needed to target various stages of the hepatitis B virus lifecycle and modulation of the immune system. This Review provides a summary of available regimens with their strengths and limitations, and highlights future therapeutic strategies to target the virus and host immune response. These new agents can hopefully lead to a finite duration of treatment, and provide a functional and durable cure for chronic hepatitis B infection.