Using defined best practices can reduce rates of central line–associated bloodstream infections (CLABSIs). Many different national initiatives aim to widely spread these evidence-based practices across medical centers. This article describes the iterative process and lessons learned by a university medical center during a 7-year initiative to decrease CLABSIs. Stakeholder buy-in and culture change are specifically highlighted as important features. The authors note that changing the culture and practice of medical and nursing staff can be difficult, taking time and perseverance. An AHRQ WebM&M perspective by Dr. Timothy Hoff discusses how to establish a safety culture.