Space travel has grown during the past 2 decades, and is expected to surge in the future with the establishment of an American Space Force, businesses specializing in commercial space travel, and National Aeronautics and Space Administration’s planned sustained presence on the moon. Accompanying this rise, treating physicians are bracing for a concomitant increase in space-related medical problems, including back pain. Back pain is highly prevalent in astronauts and space travelers, with most cases being transient and self-limiting (space adaptation back pain). Pathophysiologic changes that affect the spine occur during space travel and may be attributed to microgravity, rapid acceleration and deceleration, and increased radiation. These include a loss of spinal curvature, spinal muscle atrophy, a higher rate of disc herniation, decreased proteoglycan and collagen content in intervertebral discs, and a reduction in bone density that may predispose people to vertebral endplate fractures. In this article, the authors discuss epidemiology, pathophysiology, prevention, treatment, and future research.