This paper reviews developments in human factors and then draws from a number of “best practice” cases in studying how best to apply behavioral science principles, knowledge, and analytical tools to the engineering design or improvement of systems. Government and other commercial experiences are examined with a focus on the Navy human system integration (HSI) process. Included are discussions facilitated at a workshop session sponsored by the Transportation Research Board of the National Academies. There is general consensus that in addition to using a well-designed or proven process and doing the right things, success is dependent upon attending to a prioritized short list of critical elements. Continued focus on these elements is necessary to successfully apply human behavioral sciences effectively during design, construction, and operation of systems to improve safety, reliability, effectiveness, efficiency, and quality of life.