Planning for long-duration space flights requires consideration of complex disease prevention, behavioral health, and clinical treatment issues-issues resulting from the hazards of the space environment and from limitations to in-mission medical care. These research and development needs have prompted NASA to seek and coordinate assessment from both national and international space medicine practice as well as biomedical research communities. Review of NASA's Human Research Program Evidence Books: A Letter Report examines NASA's plans to assemble the available evidence on human health risks of spaceflight and moves forward in identifying and addressing gaps in research. Recommendations to strengthen the content, composition, and dissemination of the evidence books are intended to improve future versions of these critical documents. These evidence books should be the continuously updated knowledge base of best evidence regarding risks to human health associated with spaceflight, particularly spaceflight beyond low Earth orbit and of long duration. Such a knowledge base will serve the interests of mission planners, researchers, and ultimately the individuals who accept those risks in their role as space travelers.