This chapter explores the evolution and current practices of clinical risk management, with a particular focus on the transformative impact of the 1999 To Err Is Human report by the Institute of Medicine. This landmark publication reframed medical errors as a systemic issue rather than individual failings, sparking global efforts to improve patient safety. Drawing on foundational studies like the Harvard Medical Practice Study, the chapter highlights the report’s key findings and the widespread policy and organizational changes it inspired. The development and adoption of tools such as the Critical Incident Reporting System (CIRS) and the World Health Organization’s surgical safety checklist are examined in detail, demonstrating how structured, non-punitive approaches can effectively identify and mitigate risk. Practical examples from various clinical settings—operating rooms, ICUs, pharmacies, and maternity wards—underscore the value of standardized protocols in reducing harm. The chapter also discusses the international dissemination of patient safety strategies, including national reforms in the United Kingdom, Australia, and other countries. Finally, the role of healthcare managers is analyzed, emphasizing their responsibility in embedding safety culture, guiding the use of analytical tools, and ensuring continuous quality improvement. Together, these elements illustrate a global shift toward proactive, systemic strategies in managing clinical risk and advancing patient safety.