Health care reform presents academic health centers with an opportunity to test new systems of care, such as accountable care organizations (ACOs), that are intended to improve patients' health and well-being, mitigate the anticipated shortage in primary care providers, and bend the cost curve. In its ongoing efforts to develop an ACO, the Robert Wood Johnson Medical School, an academic health center, has found helpful a rapidly evolving competitive environment and insurers willing to experiment with new models of care. But the center has also encountered six types of barriers: conceptual, financial, cultural, regulatory, organizational, and historical. How this academic health center has faced these barriers offers valuable lessons to other health systems engaged in creating ACOs.