The general science of infection prevention and control can be applied to and adapted for a variety of settings, including kindergarten through grade 12 (K-12). Strategies can be implemented in the classroom and whole school environment to prevent a wide array of illnesses caused by both bacteria and viruses. This science brief presents findings from a review of research studies focused on school- based strategies to prevent and control respiratory and gastrointestinal infections. The studies reviewed in this brief informed and supported development of the Guidance for Preventing Spread of Infections in K-12 Schools. Previous literature reviews have been published about infection prevention in schools, and most have focused on single intervention strategies such as hand washing, cleaning and disinfection, or contact tracing. Additionally, Centers for Disease Control and Prevention (CDC) has evidence-based guidance, including the respiratory virus guidance that was taken into consideration when developing this brief. This science brief adds to existing literature by describing the current state of science for a comprehensive set of strategies to prevent spread of respiratory and gastrointestinal infections in K-12 settings.