Human factors analysis (HFE) presents a formidable contribution to quality improvement (QI) in the neonatal intensive care unit (NICU). The science behind the fundamental principles concerning the design of work systems that match the needs of the people who work in them is sound and is applied widely in other safety critical situations. Early application of HFE in NICUs has shown the usefulness of these methods for frontline teams working to improve quality, reliability, and safety. The inclusion of human factors considerations in the design of structure and process has the potential to improve outcomes for patients and families and to improve the comfort and usability of work systems for providers who work in them. New technologies and continual change must be informed and designed through the application of HFE methods and principles to realize the full potential of QI.