The Aligning Forces for Quality (AF4Q) National Program Office (NPO), funded by the Robert Wood Johnson Foundation (RWJF), was successful in designing, implementing, and managing the Foundation’s signature effort to improve the quality of health care. National program offices have traditionally provided program leadership, implementation, technical assistance, some of the grant oversight, and communications. As a vital link between funders and grantees, NPOs play a critical role. However, NPOs need time, resources, and knowledge to quickly recruit or deploy talent, and develop internal processes and systems to meet the unique needs of a funder’s program. The AF4Q experience suggests that successfully meeting evolving programmatic goals depends on the capacity to fulfill the following core competencies.