Although significant progress has been made in improving patient safety over the past decade, most health care organizations still experience persistent safety problems. In this commentary, leaders of several leading safety organizations endorse five principles for transforming hospitals and clinics into high reliability organizations. These include transparency in disclosing errors and quality problems, integration of care across teams and disciplines, engaging patients in safety, developing a culture of safety, and reforming medical education to focus on quality and safety. The lead author, Dr. Lucian Leape, was interviewed about his remarkable career in patient safety by AHRQ WebM&M in 2006.