Developing highly reliable care for patients requires changes in some traditional beliefs of medical practice, an evolution toward a "system" of health care, the disciplined application of scientific principles, modifications in the way all future providers are trained, and a fundamental understanding by leadership that quality must become a business strategy and core work, not an expense or regulatory requirement. Quality at Mayo is defined as a composite of outcomes, safety, and service. A 4-part strategic construct focusing on Culture, Infrastructure, Engineering, and Execution has been developed to guide improvement activities and to ensure a comprehensive approach to better patient care. The Mayo Clinic experience has led to a greater understanding of the leadership commitment, organizational challenges, and the breadth of initiatives necessary to achieve highly reliable care.