Inequalities in health outcomes impose substantial human and economic costs on all societies—and the relation between early adversity and lifelong well-being presents a rich scientific framework for fresh thinking about health promotion and disease prevention broadly, augmented by a deeper focus on how racism influences disparities more specifically. This review begins with an overview of advances in the biology of adversity and resilience through an early childhood lens, followed by an overview of the unique effects of racism on health and a selective review of findings from related intervention research. This article presents a framework for addressing multiple dimensions of the public health challenge—including institutional/structural racism, cultural racism, and interpersonal discrimination—and concludes with the compelling need to protect the developing brain and other biological systems from the physiological disruptions of toxic stress that can undermine the building blocks of optimal health and development in the early childhood period.