Over the past two decades, health care organizations have focused intensely on patient safety. Goals to eliminate preventable deaths and keep patients free from harm are now commonplace. Although early efforts at increasing patient safety largely focused on clinical processes and improvements at the bedside, it is now recognized that these isolated, front line tactics cannot succeed without commitment to an organizational culture of safety. Building a culture of safety is a prerequisite for high reliability performance, the ideal operating environment for health care organizations. This chapter explores the concept of a culture of safety including key components of the culture, methods to measure culture, and actionable leadership steps for culture change.