To be ready to learn, children need to be focused, engaged, and able to bounce back from setbacks. However, many children come to school with heightened or diminished physiological arousal due to exposure to poverty-related risks. While stress physiology plays a role in explaining how adversity relates to processes that support students’ cognitive development, there is a lack of studies of physiological stress response in educational settings. This review integrates relevant studies and offers future directions for research on the role of stress physiology in the school adaptation of elementary school students, focusing on these important questions: (a) What are the links between physiological stress response and learning-related skills and behaviors, and do they vary as a function of proximal and distal experiences outside of school? (b) How are school experiences associated with students’ physiological stress response and related cognitive and behavioral adaptations? (c) How can we leverage measures of students’ physiological stress response in evaluations of school-based interventions to better support the school success of every student? We hope to stimulate a new wave of research that will advance the science of developmental stress physiology, as well as improve the application of these findings in educational policy and practice.