The Keystone ICU project is a landmark achievement in patient safety. This project, funded by AHRQ, represented a collaboration between patient safety experts at Johns Hopkins University and the Michigan Hospital Association to improve patient safety in 99 intensive care units (ICUs). This article discusses implementation of the comprehensive unit-based safety program, which was the cornerstone of the project, and provides detailed information on the organizational change model used as well as the interventions that were implemented. The remarkable successes achieved by this project include near-elimination of catheter-related bloodstream infections and a significant improvement in the safety culture in participating ICUs. The project's principal investigator, Dr. Peter Pronovost, was interviewed by AHRQ WebM&M near the project's conclusion in 2005.