The authors describe the experience of 40 hospitals that participated in an Institute for Healthcare Improvement (IHI) Breakthrough Series collaboration to reduce medication errors. Participating institutions were educated in the “Model for Improvement,” a structured set of change management practices emphasizing clear identification of goals, “rapid cycle” evaluation of intermediate steps toward the goal, and a collaborative, team-oriented approach. The successful experiences of participating institutions are reviewed, as well as cases and causes of failed initiatives. The authors review the value of this systems-based, team-oriented quality improvement effort relative to traditional “blame and train” practices focused on the individual practitioner and discuss the challenges of maintaining performance gains over time.