Children are increasingly exposed to armed conflict and targeted by governmental and nongovernmental combatants. Armed conflict directly and indirectly affects children's physical, mental, and behavioral health. It can affect every organ system, and its impact can persist throughout the life course. In addition, children are disproportionately impacted by morbidity and mortality associated with armed conflict. A children's rights-based approach provides a framework for collaboration by the American Academy of Pediatrics, child health professionals, and national and international partners to respond in the domains of clinical care, systems development, and policy formulation. The American Academy of Pediatrics and child health professionals have critical and synergistic roles to play in the global response to the impact of armed conflict on children.