The detrimental impact of long duration space flight on physiological systems necessitates the development of exercise countermeasures to protect work capabilities in gravity fields of Earth, Moon and Mars. The respective rates of physiological deconditioning for different organ systems during space flight has been described as a result of data collected during and after missions on the Space Shuttle, International Space Station, Mir, and bed rest studies on Earth. An integrated countermeasure that simulates the body's hydrostatic pressure gradient, provides mechanical stress to the bones and muscles, and stimulates the neurovestibular system may be critical for maintaining health and well being of crew during long-duration space travel, such as a mission to Mars. Here we review the results of our studies to date of an integrated exercise countermeasure for space flight, lower body negative pressure (LBNP) treadmill exercise, and potential benefits of its application to athletic training on Earth. Additionally, we review the benefits of Lower Body Positive Pressure (LBPP) exercise for rehabilitation of postoperative patients. Presented first are preliminary data from a 30-day bed rest study evaluating the efficacy of LBNP exercise as an integrated exercise countermeasure for the deconditioning effects of microgravity. Next, we review upright LBNP exercise as a training modality for athletes by evaluating effects on the cardiovascular system and gait mechanics. Finally, LBPP exercise as a rehabilitation device is examined with reference to gait mechanics and safety in two groups of postoperative patients.