Despite evidence that over 40% of youth in the United States have one or more adverse childhood experiences (ACEs), and that ACEs have cumulative, pernicious effects on lifelong health, few primary care clinicians routinely ask about ACEs. Lack of standardized and accurate clinical assessments for ACEs, combined with no point-of-care biomarkers of the “toxic stress” caused by ACEs, hampers prevention of the health consequences of ACEs. Thus, there is no consensus regarding how to identify, screen, and track ACEs, and whether early identification of toxic stress can prevent disease. In this review, we aim to clarify why, for whom, when, and how to identify ACEs in pediatric clinical care. To do so, we examine the evidence for such identification; describe the efficacy and accuracy of potential screening instruments; discuss current trends in, and potential barriers to, the identification of ACEs and the prevention of downstream effects; and recommend next steps for research, practice, and policy.