In a landmark study, Felitti et al found 10 Adverse Childhood Experiences (ACEs) to be associated, in a dose-dependent manner, with the leading causes of illness and death in adults decades later. Over the subsequent 20 years, research has confirmed that trauma in early childhood, in the absence of sufficient protective caregiving, causes a frequent or prolonged stress response that is the physiological link between childhood trauma and poor adult outcomes. Schonkoff and Garner termed this “toxic stress.”ACEs harm a child's still-developing immunological system and brain explaining the findings of poor physical, emotional, and developmental health down the road. For pediatric researchers and practitioners, these data have created a 2-fold challenge: How to mitigate exposure to adversity and, critically, how to ameliorate the impacts of adversity on those exposed. In practice, this requires identification of those at risk and responses and tools to impact the trajectory.