Prevention of mother-to-child transmission (PMTCT) of hepatitis B virus (HBV) is a cornerstone of strategies aiming to eliminate this global public health threat. MTCT is now the leading route of new HBV infections worldwide, so there is an urgent need to review and enhance existing interventions. Current PMTCT programmes aim to deliver a timely birth dose (BD) HBV vaccination for all infants, together with maternal antiviral prophylaxis during pregnancy and post exposure neonatal prophylaxis with HBV immunoglobulin (HBIg) in high-risk cases. In this letter, we underline the case for relaxing and simplifying criteria for antenatal tenofovir prophylaxis. This approach is warranted on the basis that other interventions are currently limited in many settings; programmatic roll-out of BD vaccination has been poor, access to HBIG is restricted by prohibitive costs and cold-chain requirements, and maternal risk-stratification is often impractical, due to poor access to laboratory testing. An increasing body of rigorous metanalysis data, reporting antiviral use in the management of HIV and HBV infections during pregnancy, supports the efficacy and safety of tenofovir. Meaningful strides towards HBV elimination in populations at highest risk requires flexible and pragmatic use of evidence-based interventions, together with education and advocacy, to abolish neglect and long-term health inequities.