Millions of children worldwide experience acute medical events. Children’s responses to these events range from transient distress to significant posttraumatic stress disorder symptoms (PTSS). While many models suggest explanations for the development and maintenance of PTSS in adults, very few have focused on children. Current models of child PTSS are primarily restricted to the post-trauma period, thus neglecting the critical peri-trauma period when screening and preventive interventions may be most easily implemented. Research on PTSS in response to pediatric medical trauma typically examines predictors in isolation, often overlooking potentially important interactions. This paper proposes a new model utilizing the bio-psycho-social framework and focusing on peri-trauma processes of acute medical events. Understanding the relationships among bio-psycho-social factors during peri-trauma can inform early identification of at-risk children, preventive interventions, and clinical care. Recommendations for future research, including the need to examine PTSS in the context of multiple influences, are discussed.