Even before the very beginning of human space exploration, serious and reasonable concerns were expressed about exposure of humans to the microgravity of space due to the potential systemic effects on terrestrially-evolved life forms adapted to Earth gravity. Unloading of skeletal muscle, both on Earth via bed-rest experiments and during spaceflight, result in remodeling of muscle (atrophic response). As a result, decrements occur in skeletal muscle strength, fatigue resistance, motor performance, and connective tissue integrity. In addition, there are cardiopulmonary and vascular changes, including a significant decrease in red blood cell mass, that affect skeletal muscle function. This normal adaptive response to the microgravity environment may become a liability resulting in increased