The author describes five critical elements for reducing and, ultimately, preventing harm to patients-from a systems perspective. In the element called leadership and culture, leaders must advocate patient safety as a primary goal and foster an institutional culture where change that promote patient safety can occur. In internal surveillance, systems are established to actively monitor for deviations in quality and guide efforts to engineer risk of harm out of the institution's practices; they can also demonstrate absence of risk or harm. Although incident reporting can be controversial and is sometimes avoided because its use in "blame attacks," etc., it can be valuable if built on a continuous improvement approach and a system approach to error prevention. External surveillance involves the identification and response to "sentinel events," such as wrong-sided surgery, and serves to remind all those involved in care just how risky and unforgiving medical practice can be. Finally, those involved in promoting safety must believe that hazard and risk are not inevitable and can be managed. The author illustrates this approach by describing his hospital's successful efforts to prevent the rise of aspergillus infections during a major hospital construction project. The author closes by describing selected challenges and opportunities to reduce harm from a systems perspective, such as using teams, involving patients and the public, using lessons learned from other industries with strong safety cultures, and using advances in information systems for a variety of safety-oriented tasks.