Objective: Children and families presenting for care in pediatric medical settings may arrive with prior exposure to potentially traumatic events and may experience pediatric medical care as traumatic. Such experiences place children and their families at risk for traumatic stress. Trauma-informed care, which aims to minimize the impact of trauma, is recommended across pediatric medical settings. This introductory article to the current Special Issue provides an overview of traumatic stress and trauma-informed care across pediatric populations and settings, highlights key findings from articles within this Issue, and offers direction for future studies. Method: We elicited articles that focused on clinical practice approaches and novel research related to the full scope of trauma exposure and trauma-informed care practices in pediatric medical settings. Articles could include traditional research reports, case studies, quality improvement reports, and topical/systematic reviews. Results: This Special Issue includes 10 articles focused on implementation of trauma-specific screening programs, impacts of pediatric trauma on family systems, best practices in caring for children with grief, and trauma-informed interventions targeting healthcare providers. A variety of pediatric populations, such as injury, primary care, genetics, and oncology, are represented. Conclusion: Building on the articles in this Special Issue, we identify opportunities to advance research on pediatric traumatic stress and trauma-informed care. Future research should examine the impact of trauma-informed care on medical outcomes for children and families and employ community-engaged and rigorous implementation science methods to improve the reach of this care across pediatric medical settings.