Population aging, rapidly increasing costs of healthcare and the growing burden of chronic disease are challenges to health systems worldwide. To meet these challenges will require new approaches to healthcare delivery and comprehensive population health management. Within the context of healthcare reform initiatives, important innovations in delivery system organization in the United States are discussed. The innovations focused on are the Patient-Centered Medical Home (PCMH), the Accountable Care Organization (ACO) and the Population Health Management System (PHMS) combined with new payment arrangements that reward for health outcomes achieved rather than paying a fee for each service rendered. For each of these innovations, the evidence on its performance, the challenges involved, and the factors that might promote greater adoption and diffusion of successful models are reviewed. Finally, the role played by a country's political system and its associated culture, structural barriers, size and resources, incentive alignment, and leadership are discussed.