This report represents an edited version of Donald Berwick’s Plenary Address presented at the Institute for Healthcare Improvement’s 11th Annual National Forum on Quality Improvement in Health Care (December 1999). In his address to more than 3000 attendees, Berwick uses the story of the Mann Gulch Fire tragedy to frame a series of reflections on the failures of systems, organizations, and individuals who operate within them. He goes on to share his personal experience with the health care system in describing the details of his wife’s illness that required several hospitalizations, placing him at the sharp end to experience our system’s shortcomings on a daily basis. He builds on the anecdotes by describing factors that contribute to an organization’s failures, once again incorporating a number of analogies that make his delivery of content easy to grasp for novices and experts in the audience. Finally, Berwick proposes three design elements in creating a radically different and much improved health care system. They include greater access for patients to the system, improved application of science at the bedside, and better attention to the interactions between patients and the system.