After five decades of growth that has included advances in medical education and health care delivery, value cohesion, and integration of diversity, we propose an overarching mission for academic general internal medicine to lead excellence, change, and innovation in clinical care, education, and research. General internal medicine aims to achieve health care delivery that is comprehensive, technologically advanced and individualized; instills trust within a culture of respect; is efficient in the use of time, people, and resources; is organized and financed to achieve optimal health outcomes; maximizes equity; and continually learns and adapts. This mission of health care transformation has implications for the clinical, educational, and research activities of divisions of general internal medicine over the next several decades.