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To successfully exist in space, the goal of system designers today must be to provide an environment where current and future travelers may work efficiently and effectively over longer and longer periods of time. Ensuring human health and well-being involves habitability issues (e.g., resource requirements for hygiene, work, leisure), perceptual and sensory elements, biological issues and physiological and psychological factors that facilitate mental and emotional health. This overview covers the interrelations between life support engineering/human factors, the medical/ physiological factors and the psychological and social aspects of humans in space that will be key elements in the success of long-duration missions with an emphasis on a multidisciplinary approach.