Active engagement of both the designated institutional official (DIO) and the program director (PD) is essential to implement any change in graduate medical education (GME). Strategies that are established by the Accreditation Council for Graduate Medical Education or other entities are, in the end, effective only as implemented at the individual program level. The interpretation of national standards or guidelines, and the specific adaptation to the vagaries of individual institutions and programs, can lead to significant variability in implementation and potentially in outcomes. Variability occurs between programs within the same institution and between some specialty programs at different institutions. The National Initiative, sponsored by the Alliance of Independent Academic Medical Centers, was launched in 2007 to demonstrate the effectiveness of GME as a key driver to improve quality, patient safety, and cost-effectiveness of care. This report addresses (1) the key roles of both the DIO and the PD in achieving the goals of the National Initiative, (2) the challenges these goals presented to each role, and (3) some of the tactics drawn from the experiences of the National Initiative in overcoming those challenges. The experience of the National Initiative underscored the synergies of the DIO and PD roles to improve patient care while simultaneously fulfilling their critical responsibilities as institutional and program leaders in GME with even greater effectiveness.