Public health activities in the United States are delivered through multiple public and private organizations that vary widely in their resources, missions, and operations. Without strong coordination mechanisms, these delivery arrangements may perpetuate large gaps, inequities, and inefficiencies in public health activities. We examined evidence and uncertainties concerning the use of partnerships to improve the performance of the public health system, with a special focus on partnerships between public health agencies and health care organizations. We found that the types of partnerships likely to have the largest and most direct effects on population health are among the most difficult, and therefore least prevalent, forms of collaboration. High opportunity costs and weak and diffuse participation incentives hinder partnerships that focus on expanding effective prevention programs and policies. Targeted policy actions and leadership strategies are required to illuminate and enhance partnership incentives.