Motion sickness remains a persistent problem in spaceflight. The present review summarizes available knowledge concerning the incidence and onset of space motion sickness and aspects of the physiology of motion sickness. Proposed etiological factors in the elicitation of space motion sickness are evaluated including fluid shifts, head movements, visual orientation illusions, Coriolis cross-coupling stimulation, and otolith asymmetries. Current modes of treating space motion sickness are described. Theoretical models and proposed ground-based paradigms for understanding and studying space motion sickness are critically analyzed. Prediction tests and questionnaires for assessing susceptibility to space motion sickness and their limitations are discussed. We conclude that space motion sickness does represent a form of motion sickness and that it does not represent a unique diagnostic entity. Motion sickness arises when movements are made during exposure to unusual force backgrounds both higher and lower in magnitude than 1 g earth gravity.