Implications for the academic and interpersonal development of children and adolescents underpin a global political consensus to maintain in-classroom teaching during the ongoing COVID-19 pandemic. In support of this aim, the WHO and UNICEF have called for schools around the globe to be made safer from the risk of COVID-19 transmission. Detailed guidance is needed on how this goal can be successfully implemented in a wide variety of educational settings in order to effectively mitigate impacts on the health of students, staff, their families, and society. This review provides a comprehensive synthesis of current scientific evidence and emerging standards in relation to the use of layered prevention strategies (involving masks, distancing, and ventilation), setting out the basis for their implementation in the school environment.In the presence of increasingly infectious SARS-Cov-2 variants, in-classroom teaching can only be safely maintained through a layered strategy combining multiple protective measures. The precise measures that are needed at any point in time depend