This chapter reviews relationships between people, rules creating new systems and reforms in technology, and knowledge that has solidified behavioral health and performance requirements as crucial to the health and performance of long-duration mission (LDM) astronauts and those who will one day man space exploration missions. The National Aeronautics and Space Administration (NASA) mental health team also needed to explain the challenges faced by LDM astronauts and their families with more than just our opinions. NASA mission and medical leaders needed data to help them weigh the risks of the mental health needs of these astronauts and families against many other demands on budget and valuable time in training and on orbit. Human-System Interface factors affect astronaut performance primarily in the areas of work/rest schedules, and in ergonomics/including the value of privacy, as well as individualized methods for LDM training/retraining.