Humans are so successfully adapted to life on Earth and its gravity (1g), that we have devised ways to achieve escape velocity and leave that gravitational environment. The ‘weak’ force of gravity is omnipresent on Earth, modulating many biological processes and the physical-chemical interactions that underlie them. However, just how gravity affects cellular biological processes and organism behaviour is largely unknown. Transition into microgravity can elicit acute spatial disorientation and a range of autonomic symptoms, collectively defined as space adaptation syndrome (SAS). These symptoms, thought to arise from sensory-mismatching, whilst not life threatening, are unpleasant and can on occasions incapacitate. In the event of an emergency, this may place the afflicted and their colleagues in danger and prevents extra-vehicular activity (EVAs) being scheduled early in a mission. As a consequence, potential mechanisms and methods of mitigation have received much attention, despite the fact that SAS is usually transient – ameliorating over 2-3 days. SAS may however, be re-activated in novel situations such as an EVA, or when a crew member unexpectedly floats by. This sensitivity may relate to the fact that visual cues become relatively more important for spatial orientation, a feature common with a range of sensory pathologies on Earth. Indeed microgravity leads to adaptation of vestibular, somatosensory, proprioceptive and other gravitoceptive (relating to fluid distribution/pressure) mechanisms. Adaptation to microgravity is rapidly reversible (with a similar temporal profile to adaptation) on return to a 1g environment. Such acute sensory-reweighting in otherwise healthy individuals may inform interventional strategies in those whom adaptation to sensory-loss (or hyper-excitability) is inhibited. Microgravity has also been shown to retard pre-natal (e.g. vestibular projections), and post-natal development (e.g. righting behaviour and locomotion) in rodents. Intriguingly, the existence of a critical exposure g threshold or ‘time window’ remains to be determined. Exploration of these issues using analogues or the partial gravity environments of the Moon (~0.167g) and Mars (~0.38g) may inform understanding, providing insights for (developmental) rehabilitation and sensory augmentation strategies on Earth. Production of a consistent ‘artificial’ 1g environment might mitigate sensori-motor changes, however significant engineering challenges exist. Imposition of hypergravity for brief periods has been proposed as a potential countermeasure. However, determination of the tolerability, relative efficacy, and the required ‘effective dose’ in terms of both magnitude and exposure (duration x frequency) remain to be determined, which again may have possible terrestrial applications. In addition to vestibular changes, somatosensory and proprioceptive mechanisms including static and dynamic position sense demonstrate adaptation during prolonged microgravity exposure. These changes must be integrated in order to perform a range of tasks, from eating and personal hygiene, to complex docking manoeuvres (with or without visual contact). As a result accurate and appropriate prediction of exocentric motion and egocentric force production and/or motion are required. Intriguingly, there is recent evidence that Newtonian laws of motion are ‘hard wired’ evident even in microgravity, offering critical insights into Earth bound sensory-motor function. Microgravity provides an opportunity to differentiate mechanisms that depend upon relative movement with, or without respect to a gravitational vector. On Earth, the effect of gravity is so ubiquitous that its effects are difficult to differentiate, or are simply overlooked. However, it may obscure or modulate other operative physiological mechanisms. Microgravity experiments were used to disprove Barany’s (Nobel Prize winning) convection hypothesis as the operative mechanism for caloric stimulation, a routine vestibular clinical test that evokes perception of rotation without actual movement. Gravity also appears to play a vital role in the perception of size, distance and inclination. Work is in its infancy but promises much, particularly as these processes may have been a key factor in humankind’s success in inhabiting vast swathes of the globe, and one of the major reasons for astronaut, rather than robotic exploration beyond it. Micro- and partial gravity experiments offer opportunities to understand the fundamental mechanisms that underlie the perception of, interaction with, and navigation on Earth. Critically, it also offer insights into approaches to ameliorate spatial disorientation and imbalance, thereby reducing falls risk, the UK’s leading cause of injury-related deaths in older adults, and a major precipitator of socio-economic inactivity in an ageing population.