Clinicians and health systems are facing widespread challenges, including changes in care delivery, escalating health care costs, and the need to keep up with rapid scientific discovery. Reorganizing U.S. health care and changing its practices to render better, more affordable care requires transformation in how health systems generate and apply knowledge. The "rapid-learning health system"-posited as a conceptual strategy to spur such transformation-leverages recent developments in health information technology and a growing health data infrastructure to access and apply evidence in real time, while simultaneously drawing knowledge from real-world care-delivery processes to promote innovation and health system change on the basis of rigorous research. This article describes an evolving learning health system at Group Health Cooperative, the 6 phases characterizing its approach, and examples of organization-wide applications. This practical model promotes bidirectional discovery and an open mind at the system level, resulting in willingness to make changes on the basis of evidence that is both scientifically sound and practice-based. Rapid learning must be valued as a health system property to realize its full potential for knowledge generation and application.