Systems integration in health care applies systems engineering and risk management principles to improve patient care. A systems perspective recognizes that health care is a complex adaptive system, comprising many components with multifaceted interrelationships. Systems engineering and risk management seek to understand the system as a whole, its components, and their interrelationships. Simulation provides a medium, through which patient care experiences can be recreated, to systematically observe, modify, and evaluate health care delivery. Simulation can also be used to explore hazards and threats, even before they impact patients, and to help us understand and reinforce appropriate actions and resources. We will introduce different systems engineering frameworks and provide examples of how simulation has been, and could be, integrated with these frameworks in pediatric emergency medicine. By integrating our discoveries in simulation with the infrastructure for change, we have the opportunity to create lasting change in our emergency departments and across our health care organizations.