Leaders of health care organizations are no longer pursuing incremental changethey are seeking breakthroughs in improvement. To achieve these breakthroughs, organizations must adopt the strategies and tactics of high reliability organizations. In recent years, the science and understanding of HROs has evolved into a codified set of operating components. This chapter explores the underlying principles of HROs, the translation of these concepts to health care, and their real-world implementation within a health care delivery system.