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Our goal is to review a number of methodologies which have been used to improve safety in healthcare since the release of the Institute of Medicine report in 1998 which documented that error was a significant cause of mortality in the USA. Multifaceted approaches have each led to reduction in error. Methods for error reduction included in this review are “Just Culture,” increased transparency and accountability, error reporting and investigation, second-victim programs, training in quality and safety methods, standardization and bundles, electronic health records, computerized order entry, barcode scanning, clinical decision support, predictive analytics, and situational awareness. Newer fields with the potential to improve patient safety include human factors engineering, indication-based prescribing, and Safety II. While each intervention has led to incremental improvement, continued expansion of these programs is necessary to eliminate medical error.