This article describes Dana-Farber Cancer Institute’s (DFCI) efforts at creating a "Just Culture," which were motivated in part by two tragic patient outcomes. The authors discuss the principles that focus on a culture of safety and how these principles become incorporated into practice. They also share practical lessons, case studies, and methods to evaluate the impact of the new principles over time. An AHRQ WebM&M perspective written by two leaders at DFCI also discusses the organizational change that occurred in the wake of this institution's highly publicized errors.