ABSTRACT: In this review, we discuss recent research in the field of human skeletal muscle protein metabolism characterizing the acute regulation of mammalian target of rapamycin complex (mTORC) 1 signaling and muscle protein synthesis (MPS) by exercise, amino acid nutrition, and aging. Resistance exercise performed in the fasted state stimulates mixed MPS within 1 h after exercise, which can remain elevated for 48 h. We demonstrate that the activation of mTORC1 signaling (and subsequently enhanced translation initiation) is required for the contraction-induced increase in MPS. In comparison, low-intensity blood flow restriction (BFR) exercise stimulates MPS and mTORC1 signaling to an extent similar to traditional, high-intensity resistance exercise. We also show that mTORC1 signaling is required for the essential amino acid (EAA)–induced increase in MPS. Ingestion of EAAs (or protein) shortly after resistance exercise enhances MPS and mTORC1 signaling compared with resistance exercise or EAAs alone. In older adults, the ability of the skeletal muscle to respond to anabolic stimuli is impaired. For example, in response to an acute bout of resistance exercise, older adults are less able to activate mTORC1 or increase MPS during the first 24 h of postexercise recovery. However, BFR exercise can overcome this impairment. Aging is not associated with a reduced response to EAAs provided the EAA content is sufficient. Therefore, we propose that exercise combined with EAA should be effective not only in improving muscle repair and growth in response to training in athletes, but that strategies such as EAA combined with resistance exercise (or BFR exercise) may be very useful as a countermeasure for sarcopenia and other clinical conditions associated with muscle wasting.