This article proposes a framework for how early experiences and environmental influences affect the genetic predispositions affecting developing brain architecture and long-term health. It also suggests that many adult diseases should be viewed as developmental disorders, and that persistent health disparities associated with poverty, discrimination, or maltreatment could be reduced by the alleviation of toxic stress in childhood. In turn, it calls for pediatricians to serve as both front-line guardians of healthy child development, and strategically positioned community advocates for educational achievement, economic productivity, responsible citizenship, and lifelong health.