Situations such as recovery from injury or illness require otherwise healthy humans to undergo periods of disuse, which lead to considerable losses of skeletal muscle mass and, subsequently, numerous negative health consequences. It has been established that prolonged disuse (>10 days) leads to a decline in basal and postprandial rates of muscle protein synthesis, without an apparent change in muscle protein breakdown. It also seems, however, that an early and transient (1–5 days) increase in basal muscle protein breakdown may also contribute to disuse atrophy. A period of disuse reduces energy requirements and appetite. Consequently, food intake generally declines, resulting in an inadequate dietary protein consumption to allow proper muscle mass maintenance. Evidence suggests that maintaining protein intake during a period of disuse attenuates disuse atrophy. Furthermore, supplementation with dietary protein and/or essential amino acids can be applied to further aid in muscle mass preservation during disuse. Such strategies are of particular relevance to the older patient at risk of developing sarcopenia. More work is required to elucidate the impact of disuse on basal and postprandial rates of muscle protein synthesis and breakdown. Such information will provide novel targets for nutritional interventions to further attenuate muscle disuse atrophy and, as such, support healthy aging.