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“Cross-sector collaboration is increasingly relied upon to tackle society’s pressing and intractable problems. Chief among societal problems are unfavorable structural and social determinants of health. The ability to positively change these health determinants rests on the collaborative processes and structures of governance across diverse sectors in society. The purpose of this article is to present a conceptual framework that sheds light on the basic requirements of cross-sector collaboration for social change to promote the health of populations. A search for theoretical articles on cross-sector collaboration in the fields of public administration and public health was conducted within the journal databases ABI/INFORM Complete and MEDLINE. This search strategy was supplemented by an internet search of the grey literature for high-profile models of cross-sector collaboration. The conceptual framework builds on previous scholarly work by placing emphasis on five essential conditions for collective impact, and on the pivotal role of collective learning. Collective learning, at the basis of planning and taking action, is at the core of effective cross-sector initiatives, specifically because of its critical role in constantly adapting strategies to changing circumstances and unanticipated situations within complex socio-ecological systems.”