The purpose of this paper is to briefly review some of the effects of reduced muscle use on the structure and function of human and animal skeletal muscle. A loss in muscle strength has been observed in astronauts after space flight. On Earth joint fixation of human limbs results in losses in muscle mass, in the cross-sectional area of both fiber types, and in the activities of mitochondrial enzymes. Methods that reduce muscular activity of animals also produce muscle atrophy. Fixation of the limb joints in position where the muscles are maintained less than resting length results in an atrophy in slow-twitch muscle. Associated with this atrophy are decreases in sarcomere number, fiber cross-sectional area, protein synthesis, and insulin responsiveness for the uptake of 2-deoxyglucose by muscle. Suspension of animals in a horizontal or head-down position is also a method being used currently for unloading muscles and producing alterations in development. In the future, the animal and human model should identify the mechanisms responsible for a decrease in muscle function when the muscle undergoes a decrease in usage.