Two of the leaders in the patient safety movement, Lucian Leape and Donald Berwick, share their perspectives on the progress made since the Institute of Medicine’s (IOM) release of To Err is Human. They summarize the shifts in thinking that have occurred, from blaming individual physicians towards targeting systems as a method to improve both quality and safety. Discussion includes the evolution of error prevention strategies, the role of interested stakeholders in the safety movement, and the impact of implementing best practices. Barriers to ongoing progress are also shared, including the increasing complexity of health care, a tradition of autonomy in care, and the current financial incentive systems. The authors provide a vision for the next five years with expectations for rapid change in adoption of electronic medical records, teamwork training, and full disclosure to patients. While they applaud several efforts and initiatives, such as the growth of AHRQ-funded research, the authors call for a rededication of providers and policymakers to the cause of patient safety, promoted by increased funding, better alignment of incentives, and the setting of ambitious but achievable safety targets.