The relation of stress hormones and activity in stress response systems to the development of aspects of cognition and behavior important for educational achievement and attainment is examined from the perspective of the developmental psychobiological model. It is proposed that research in neuroendocrinology supports three general conclusions, namely (1) that there is a neuroscientifically definable optimal level of stress arousal in children against which various curricula and teaching and learning activities can be examined; (2) that consideration of the time course of stress arousal indicates that optimal levels of stress arousal are temporally limited and can be matched to specific instructional activities; and (3) that alterations to stress response systems through processes of allostasis and allostatic load, particularly for children facing early psychosocial disadvantage, can impair the flexible regulation of stress response systems needed for effective learning in school.