Adversity in childhood has effects on mental and physical health, not only in childhood but across the lifespan. A chief task of our research has been to define the pathways by which childhood experience has these surprising health outcomes, often decades later. The concept of allostatic load, which refers to dysregulations across major biological regulatory systems that have cumulative interacting adverse effects over time, provides a mechanism for understanding these relations and defining specific pathways. To chart these pathways, we examine early childhood socioeconomic status, family environment, and genetic predispositions as antecedents to socioemotional functioning/psychological distress; and neural responses to threat that have downstream effects on major stress regulatory systems, ultimately culminating in risks to mental and physical health outcomes. This integrative approach to investigating the impact of childhood experience on adult health outcomes illustrates the significance of multilevel integrative approaches to understanding developmental psychopathology more generally.