The stimulation of protein synthesis that occurs in skeletal muscle in response to either nutrient intake or a bout of resistance exercise requires activation of the protein kinase known as the mechanistic (a.k.a. mammalian) target of rapamycin in complex 1 (mTORC1). The activation state of mTORC1 is controlled by several upstream signaling pathways that function in a combinatorial manner to integrate positive (e.g., re-feeding and/or resistance exercise) or negative (e.g., inactivity or glucocorticoid treatment) inputs to the kinase. For example, amino acids and insulin act through independent pathways to activate mTORC1 in an additive manner. In contrast, hindlimb immobilization attenuates the stimulatory effect of leucine on mTORC1 activity in muscle. A growing body of evidence implicates a protein known as REDD1 (regulated in development and DNA damage response 1) as a critical regulator of mTORC1 signaling, and in a variety of studies REDD1 expression has been shown to be inversely proportional to the activation state of mTORC1. For example, REDD1 abundance is reduced and mTORC1 signaling is elevated after a bout of resistance exercise, but the opposite effects are observed after endurance exercise. Moreover, compared with freely fed rats, REDD1 abundance is elevated and mTORC1 signaling is reduced after an overnight fast, and re-feeding rapidly reverses both effects. The important role played by REDD1 in controlling mTORC1 activity is emphasized in studies demonstrating that both re-feeding and muscle contraction activate mTORC1 signaling to a significantly greater extent in muscle of REDD1 deficient mice compared with wildtype mice. This presentation will focus on the signaling pathways through which amino acids, insulin, and resistance exercise act to activate mTORC1 as well as the role of REDD1 in governing the stimulatory effect of these inputs on the kinase. Work in the author’s laboratory is supported by NIH grants DK13499, DK15658, and DK094141.