Human factors is a critical discipline for human spaceflight. Nearly every human factors research area is relevant to space exploration-from the ergonomics of hand tools used by astronauts, to the displays and controls of a spacecraft cockpit or mission control workstation, to levels of automation designed into rovers on Mars, to organizational issues of communication between crew and ground. This chapter focuses more on the ways in which the space environment (especially altered gravity and the isolated and confined nature of longduration spaceflight) affects crew performance and thus has specific novel implications for human factors research and practice. We focus on four aspects of human performance: neurovestibular integration, motor control and musculoskeletal effects, cognitive effects, and behavioral health. We also provide a sampler of recent human factors studies from the National Aeronautics and Space Administration.Thi s chapter looks at exploration of space from a human factors perspective, with a focus on the astronaut crew as the primary user population of interest. Like other complex work domains such as aviation, air traffic management, health care, homeland security, and vehicle control, space exploration is a large-scale sociotechnical work domain characterized by complexity, dynamism, uncertainty, and risk in real-time operational contexts Nearly the entire gamut of human factors issues-for example, human-automation interaction, telerobotics, display and control design, usability, anthropometry, biomechanics, safety engineering, emergency operations, maintenance human factors, situation awareness, crew resource management, methods for cognitive work analysis, and habitability-are applicable to astronauts, mission control, operational medicine, spacecraft designers, manufacturing and assembly operations, and space suit designers as they are in other work domains (Connors, Harrison, & Akins, 1985Harrison, 2001;Morphew, Balmer, & Khoury, 2001;Rathjen et al., 2008). The human exploration of space also has unique challenges of particular interest to human factors research and practice. This chapter provides an overview of those issues and reports on some of the latest research results as well as the latest challenges still facing the field.