As the field of patient safety matures, emphasis is shifting from targeting specific issues to shaping safer systems, with the goal of minimizing a broad range of preventable harms. Integrating human factors engineering (HFE) principles is central to this effort. This systematic review—derived from a review originally published in the AHRQ Making Healthcare Safer II report—describes the theoretical basis of HFE and gives an overview of specific HFE techniques used in patient safety. Through a series of case studies, the article also gives practical insights into how HFE principles can be used to design safer devices and work environments and prospectively identify safety hazards. Dr. Donald Norman, one of the founders of the HFE field, was interviewed for AHRQ WebM&M in 2006.