Since the earliest days of manned space flight, the acceleration required for a space vehicle to reach orbit and to return to Earth has presented a physiological challenge to the vehicle’s occupants. Even modest levels of sustained acceleration may have profound effects on the cardiovascular and respiratory systems, resulting in reduced cerebral perfusion, pulmonary ventilation-perfusion mismatch and desaturation of arterial blood. Whilst improvements in rocketry resulted in a reduction in acceleration exposure during the days of the US Space Shuttle programme, the advent of innovative space vehicles associated with ‘space tourism’ may well promote a return to higher levels of acceleration. Furthermore, the passengers of future vehicles may comprise a population group far less tolerant to acceleration than the specially medically selected astronauts of the early space programme. In this presentation, the physiological challenges of sustained acceleration will be described, as well as the potential countermeasures. Acceleration levels in various space vehicles during launch and re-entry will be considered, together with the physiological burden of short or long duration microgravity exposure prior to re-entry acceleration.