During spaceflight missions, astronauts work in an extreme environment with several hazards to physical health and performance. Exposure to microgravity results in remarkable deconditioning of several physiological systems, leadingto impaired physical condition and human performance, posing a major risk to overall mission success and crew safety.Physical exercise is the cornerstone of strategies to mitigate physical deconditioning during spaceflight. Decades ofresearch have enabled development of more optimal exercise strategies and equipment onboard the InternationalSpace Station. However, the effects of microgravity cannot be completely ameliorated with current exercisecountermeasures. Moreover, future spaceflight missions deeper into space require a new generation of spacecraft,which will place yet more constraints on the use of exercise by limiting the amount, size, and weight of exerciseequipment and the time available for exercise. Space agencies are exploring ways to optimize exercise countermeasuresfor spaceflight, specifically exercise strategies that are more efficient, require less equipment, and are less timeconsuming.Blood flow restriction exercise is a low intensity exercise strategy that requires minimal equipment and canelicit positive training benefits across multiple physiological systems. This method of exercise training has potential asa strategy to optimize exercise countermeasures during spaceflight and reconditioning in terrestrial and partial gravityenvironments.