Healthcare leaders agree on the logic behind population health: that the focus of a care delivery system should be on keeping patient populations healthy rather than waiting to treat illness. Yet transitioning away from single-patient, episodic care is a major economic and organizational challenge for hospitals and health systems. They must revamp the roles of physicians, midlevels, and care team providers; implement data analytics solutions and learn to incorporate the findings; negotiate risk-based payment agreements with payers and partners—all at the same time. The magnitude of change, and the risk of getting it wrong, is enormous. At this Roundtable, three top accountable care organization executives discussed the challenges of engineering changes in systems of care to enable the shift toward data-assisted evidence-based practice, a culture of wellness, and, for healthcare organizations, to ensure sustainable finances.