Gravity has been an ever-existing force impacting various processes since the beginning of time. Biological properties of living organisms change when the gravitational force is altered, and not surprisingly, these changes are perceived from cellular to organismal levels. Variations in gravitational levels induce adaptive responses that influence dynamic physiological functions. In a microgravity environment where weightlessness is experienced, astronauts often suffer from space motion sickness, cardiovascular deconditioning, bone demineralization, muscle atrophy, as well as pooling and redistribution of fluids in the upper parts of the body. Additionally, indirect effects mediated by fluid shear stress and hydrostatic pressure strongly affect systems both in vitro and in vivo. In this review, we reiterate some interesting data that has been obtained from studies conducted in both microgravity and hypergravity and provide key mechanistic insights that could be responsible for the continuum of physiological changes observed in these conditions. We have mainly focused on long-duration space orbiting experiments rather than short-term parabolic flights and sounding rockets. Even after more than 500 missions, space is still not a place for either regular visits or habitation largely due to the challenges posed to normal growth and development of organisms, which is further complicated by the lack of successful and reliable countermeasures. Hence, we reinstate the use of artificial gravity simulations in tackling space-incurred physiological disturbances. © 2020 IAA