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There is currently no known cure for hepatitis B virus (HBV) infection, and HBV remains a major public health burden in the United States. The US Department of Health and Human Services has established a Viral Hepatitis National Strategic Plan with the goal of eliminating HBV infection in the United States by the year 2030. This goal will be achieved by reducing the incidence of new HBV infections by 90% and mortality by 65%, with a main focus on prevention of HBV infection through vaccination. Currently, 4 HBV vaccines (excluding bivalent vaccines) are available in the United States for use in adults, including Heplisav-B, which was approved by the FDA in November 2017 for use in adults 18 years and older. All 4 HBV vaccines are equally recommended as options for the prevention of HBV infection by the Advisory Committee on Immunization Practices. This article provides an overview of emerging considerations based on CDC recommendations and new clinical data around HBV vaccines, as well as the potential of Heplisav-B in fulfilling unmet needs that currently exist in the HBV prevention landscape.