Acute skeletal muscle disuse results in the rapid loss of skeletal muscle strength, mass, and the onset of an insulin-resistant phenotype. Whether these initial physiological responses are pro-adaptive or subversive in nature remains contentious; however, what is clear is that a protracted state of skeletal muscle disuse precipitates metabolic disease. Whilst nutritional and resistive exercise are effective non-pharmacological means to attenuate or even prevent muscle disuse atrophy, in many clinical scenarios patients are functionally impaired, and unable to participate in loading activities. Thus, nutritional intervention remains one of the most viable and scalable means to combat muscle disuse atrophy in the clinical setting. A common and reproducible signature of muscle disuse atrophy is the decline in fasted and fed rates of muscle protein synthesis. These declines result in a negative state of net muscle protein balance that ultimately induces muscle loss. Given the anabolic influence of essential amino acids, particularly the branched-chain amino acid leucine, towards rates of muscle protein synthesis, the impact of dietary amino acid manipulations rich in leucine on muscle protein turnover has received significant experimental attention. There is also data to suggest that supplementation with omega-3 fatty acids enhances rates of muscle protein synthesis in response to amino acid feeding. In this talk, the cellular and molecular mechanisms underpinning muscle disuse atrophy in humans will be summarized followed by the examination of recent data related to how muscle loading, leucine, and omega-3 fatty acids can act alone as well as in concert to enhance muscle anabolism. Specific emphasis will be placed on data generated in humans but the role of these nutritional compounds in regulating muscle protein turnover in complementary pre-clinical and cell-based systems will also be discussed.