Despite great effort, health care organizations are still learning how to identify safety problems, especially with regard to proactively detecting latent errors before patients are harmed. Prior studies have shown that no single method can unearth all safety problems within an organization, forcing leaders to rely on multiple complementary sources of data. In this report, the authors present a framework for developing a comprehensive picture of safety at the organizational level. Drawing on principles used by high reliability organizations in other industries, the framework encompasses five domains of safety: past harm (retrospectively identifying safety issues, such as through incident reports), reliability (ensuring adherence to appropriate processes of care), sensitivity to operations (prospectively identifying safety problems), anticipation and preparedness (maintaining safety culture and using checklists to avert common complications), and learning from safety events. The lead author of the report, Prof. Charles Vincent, was interviewed by AHRQ WebM&M in 2012.