The health care market dynamics that supported and directed the growth and development of Academic Health Centers (AHCs) have changed dramatically in the last 10 years. AHCs are struggling to adapt to new reimbursement mechanisms and to compete effectively for limited dollars, but are constrained by administrative and governance structures that are slow to evolve. Their multiple missions, including education, research, and care for complex patients and underserved populations, are at risk. Although most recognize the need for substantive reorganization, available resources and market specifics vary dramatically from one AHC to another. The current approaches to adaptation by four AHCs are described, along with some of the unique challenges confronted by academic pediatric programs.