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This article addresses the growing problem of antisocial behavior in schools and its impact on safety, effectiveness, and ecology. We describe the factors leading to the development of antisocial behavior in children and youth. We explore the relationship between early investment in an antisocial behavior pattern and later negative outcomes including school failure, delinquency, and violence. The article also focuses on best practices in the areas of screening and early intervention for antisocial children and youth and those who are at risk for adopting this behavior pattern. Recommendations are made regarding research-based practices, tools, and approaches in both screening and intervention. A model for integrated approaches to school-based prevention of antisocial behavior is presented and the implications of such are discussed.