Fewer than 1% of chronic hepatitis B virus infections per year are cured with antiviral treatment. This creates a need for long-term treatment, which poses challenges for patients and health systems. Because cure is accompanied by recovery of antiviral immunity, a combination of direct-acting antiviral agents and immunotherapy are likely to be required. Extensive efforts have been made to identify determinants of the failed immune response to hepatitis B virus in patients with chronic infection. We review mechanisms of immune dysfunction in patients with chronic hepatitis B virus infection, immunotherapy strategies in development, and the challenges associated with successful implementation of immunotherapy.