Protecting and sustaining children’s environmental health in today’s world requires a systems understanding of the many factors (biological, chemical, physical, and social) that interact during critical windows of development to impact a child’s ultimate health and well-being. We are learning how intrauterine and neonatal environmental factors set the stage for lifelong health, and are beginning to understand the epigenetic and molecular mechanisms through which intrauterine stressors such as under-nutrition, toxicant exposure, and social stress may alter developmental programming. Effective public health interventions that both protect and promote children’s environmental health require a systems understanding of these complexities, and better methods for assessing cumulative risks that may accrue across the developmental continuum. This symposium brings together the interdisciplinary expertise in developmental and reproductive toxicology, epidemiology, risk analysis, and children’s health needed to develop holistic, life course models for children’s environmental health protection.  Lessons learned from longitudinal cohort studies linking prenatal and childhood environmental exposures to abnormal birth outcomes and child health along the life course continuum, and strategies for translating the research results into guidance for policy-makers , health care providers, and parents.