Alcoholism and acquired immune deficiency syndrome are associated with severe muscle wasting. This impairment in nitrogen balance arises from increased protein degradation and a decreased rate of protein synthesis. The regulation of protein synthesis is a complex process involving alterations in the phosphorylation state and protein-protein interaction of various components of the translation machinery and mammalian target of rapamycin (mTOR) complexes. This review describes mechanisms that regulate protein synthesis in cultured C2C12 myocytes following exposure to either alcohol or human immunodeficiency virus antiretroviral drugs. Particular attention is given to the upstream regulators of mTOR complexes and the downstream targets which play an important role in translation. Gaining a better understanding of these molecular mechanisms could have important implications for preventing changes in lean body mass in patients with catabolic conditions or illnesses.