This article is part of a larger body of work entitled, "The Impact of Sex and Gender on Adaptation to Space." It was developed in response to a recommendation from the 2011 National Academy of Sciences Decadal Survey, "Recapturing a Future for Space Exploration: Life and Physical Sciences for a New Era," which emphasized the need to fully understand sex and gender differences. In this article, our workgroup-consisting of expert scientists and clinicians from academia and the private sector-investigated and summarized the current body of published and unpublished human research performed to date related to sex- and gender-based differences in behavioral adaptations to human spaceflight. This review identifies sex-related differences in: (1) sleep, circadian rhythms, and neurobehavioral measures; (2) personality, group interactions, and work performance and satisfaction; and (3) stress and clinical disorders. Differences in these areas substantially impact the risks and optimal medical care required by space-faring women. To ensure the health and safety of male and female astronauts during long-duration space missions, it is imperative to understand the influences that sex and gender have on behavioral health changes occurring during spaceflight.