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(N Engl J Med. 2018;378:952–953)In this editorial, the author discusses a recent study regarding the use of tenofovir disoproxil fumarate (TDF) prophylaxis and vaccination to help alleviate the increasing disease burden of hepatitis B virus (HBV) infection in countries eligible for Global Vaccine Alliance support. In these countries, HBV infection during the neonatal period and childhood remains the leading source of new chronic infections. An estimated 1% of newborns annually (>365,000 newborns) are infected at birth in sub-Saharan Africa. Although the first dose of the vaccine is scheduled to occur at 5 weeks, as per the Expanded Program on Immunization (EPI), only 48% of countries report actually administering the vaccine at birth.