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Serious events within healthcare occur daily exposing the failure of the system to safeguard patient and providers. The complex nature of healthcare contributes to myriad ambiguities affecting quality nursing care and patient outcomes. Leaders in healthcare organizations are looking outside the industry for ways to improve care because of the slow rates of improvement in patient safety and insufficient application of evidenced-based research in practice. Military and aviation industry strategies are recognized by clinicians in high-risk care settings such as the operating room, emergency departments, and intensive care units as having great potential to create safe and effective systems of care. Complexity science forms the basis for high reliability teams to recognize even the most minor variances in expected outcomes and take strong action to prevent serious error from occurring. Cultural and system barriers to achieving high reliability performance within healthcare and implications for team training are discussed.