The East Baltimore Revitalization Project, a fifteen-year, $800 million redevelopment initiative, seeks to transform a struggling area of the city near Johns Hopkins Hospital. A unique partnership of the Johns Hopkins University and Johns Hopkins Medical Institutions and the Annie E. Casey Foundation is supporting the City of Baltimore in this effort, which will focus on improving the lives of area residents as well as on traditional “bricks and mortar” activity. The article discusses both the opportunities and the challenges of the project, which is still at an early stage. The partners expect that the project will offer important lessons for rebuilding impoverished urban neighborhoods. It is also hoped that the project will provide a road map for crafting and achieving important benefits for neighborhood residents and the broader community, particularly in the form of jobs and workforce development.