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Provides an overview of the essential role of teams and teamwork in enhancing organizational performance and building multi-sector collaborations and partnerships in population health. Following deliberate, evidence-based methods for effective collaboration, identifies and discusses several key factors that can only be addressed through cross-sector efforts. These factors include the social determinants of health, complexity, context, and societal resistance. Introduces the Collective Impact Model, designed to tackle entrenched, socially complex issues, as an evidence-based model for effective, large scale, sustainable change.