Reforms in the public health infrastructure such as those called for in recent Institute of Medicine reports require stakeholder engagement on different levels than traditional grass-roots community work. The Turning Point Initiative, funded by The Robert Wood Johnson Foundation, involves 21 state-wide partnerships established for systems change and focused in specific areas of public health innovation and policy development. These partnerships represent a different model of strategic alliances and relationship-building than has been previously described in the literature on community-level and health-promotion collaborations. This article utilizes qualitative data to illustrate the ways in which state-level partnerships for systems change both confirm and extend previous models. Findings indicate that state-level public health partnerships share many of the challenges and opportunities of locally-based and health-promotion-oriented partnerships. Collaboration at the state level, however, involves more attention to organizational alliances, coordination of institutional change, and strategic responses to political changes. These partnerships depend on a combination of interpersonal skills, material resources, and organizational savvy to manage complex planning and implementation processes. Influencing policy development and organizational redesign in public health systems requires nuanced understanding of the opportunities provided by various kinds of organizational partners.