In the synergistic evolution of their research, educational, and clinical programs, the University of Pittsburgh (Pitt) School of Medicine (SOM) and the University of Pittsburgh Medical Center (UPMC) have followed one core principle: What is good for one is good for both. The collaboration is underpinned by UPMC's commitment to its community mission, including support for the academic and research objectives of the SOM. UPMC's conceptual origin was fostered by its experience with Western Psychiatric Institute and Clinic in the 1970s. Over time, UPMC acquired other hospitals through merger and negotiation and, by 2008, had grown into a $7 billion global health enterprise. From the outset, the senior leaders of both UPMC and Pitt committed to collaborative decision making on all key issues. Under this coordinated decision-making model, UPMC oversees all clinical activity, including that from a consolidated physicians' practice plan. Pitt remains the guardian of all academic priorities, particularly faculty-based research. UPMC's steady financial success underpins the model. A series of interrelated agreements formally defines the relationship between Pitt and UPMC, including shared board seats and UPMC's committed ongoing financial support of the SOM. In addition, the two institutions have jointly made research growth a priority. The payoff from this dynamic has been a steadily growing Pitt research portfolio; enhanced growth, visibility, and stature for UPMC, the SOM, and Pitt as a whole; and the sustained success of UPMC's clinical enterprise, which now has an international scope. Given the current stagnation in the National Institutes of Health budget, the Pitt–UPMC experience may be instructive to other academic health centers.