Childhood adversity is prevalent in the USA, affecting at least half of all children and youth. Growing awareness of its prevalence and harmful effects on individual health and development over the lifespan has prompted considerable interest among policymakers, program leaders, and other stakeholders in screening individual children for adversity as a first step in preventing and mitigating its negative effects. Given the vulnerability of this population, concerted efforts first should be made to ensure screening for adversity is beneficial to children and minimizes potential harm. Of particular concern is widespread use of screening tools that define adversity narrowly, failing to account for social and structural inequities (e.g., poverty, discrimination, forcible separation from a parent) or to take a child's trauma symptoms, overall development, strengths, and culture into account. Furthermore, screening in the absence of a system for referral and treatment risks being ineffective, and even harmful, to children and their families. This paper reviews major challenges related to developing and selecting tools to screen for childhood adversity, and offers recommendations for a comprehensive, strengths-based, trauma-informed screening approach that incorporates sensitivity to a child's development, environment, and culture.