Anesthesiology has long stood at the forefront of patient safety, transforming one of medicine’s highest-risk specialties into a model for error reduction, reliability, and safe system design. This chapter traces the evolution of patient safety in anesthesiology—from early crisis-driven reforms to the modern era of data analytics, simulation, and human factors engineering. It highlights how anesthesiologists apply systems thinking to prevent harm, manage crises, and improve outcomes across the perioperative continuum. This chapter explores key concepts including checklist-based safety interventions, closed claims analysis, and the role of organizational culture in sustaining safety performance. It emphasizes anesthesiologists’ leadership in developing safety protocols, fostering team communication, and implementing continuous quality improvement programs. As healthcare grows more complex, the anesthesiologist’s vigilance now extends beyond the operating room—into technology design, risk management, and institutional safety strategy—defining them as essential architects of a safer healthcare system.