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Four decades of early childhood policy and program development indicate that evidence-based interventions can improve life outcomes, and dramatic advances in the biological and behavioral sciences now provide an opportunity to augment those impacts. The challenge of reducing the gap between what we know and what we do to promote the healthy development of young children is to view current best practices as a starting point and to leverage scientific concepts to inspire fresh thinking. This article offers an integrated, biodevelopmental framework to promote greater understanding of the antecedents and causal pathways that lead to disparities in health, learning, and behavior in order to inform the development of enhanced theories of change to drive innovation in policies and programs.