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At the beginning of the 21st century, multiple and diverse social entities, including the public (consumers), private and nonprofit healthcare institutions, government (public health) and other industry sectors, began to recognize the limitations of the current fragmented healthcare system paradigm. Primary stakeholders, including employers, insurance companies, and healthcare professional organizations, also voiced dissatisfaction with unacceptable health outcomes and rising costs. Grand challenges and wicked problems threatened the viability of the health sector. American health systems responded with innovations and advances in healthcare delivery frameworks that encouraged shifts from intra- and inter-sector arrangements to multi-sector, lasting relationships that emphasized patient centrality along with long-term commitments to sustainability and accountability. This pathway, leading to a population health approach, also generated the need for transformative business models. The coproduction of health framework, with its emphasis on cross-sector alignments, nontraditional partner relationships, sustainable missions, and accountability capable of yielding return on investments, has emerged as a unique strategy for facing disruptive threats and challenges from nonhealth sector corporations. This chapter presents a coproduction of health framework, goals and criteria, examples of boundary spanning network alliance models, and operational (integrator, convener, aggregator) strategies. A comparison of important organizational science theories, including institutional theory, network/network analysis theory, and resource dependency theory, provides suggestions for future research directions necessary to validate the utility of the coproduction of health framework as a precursor for paradigm change.