Multiple lines of evidence suggest that cytokines influence different physiologic functions of skeletal muscle cells, including anabolic and catabolic processes and programmed cell death. Cytokines play an important role not only in muscle homeostasis, therefore, but also in the pathogenesis of different relevant clinical conditions characterized by alterations in protein metabolism. Recently discovered cytokines, such as ciliary neurotrophic factor and growth/differentiation factor-8, as well as the more studied tumor necrosis factor-alpha, interleukin-1, interleukin-6, and the interferons, have been implicated in the regulation of muscle protein turnover. Their postreceptor signaling pathways, proteolytic systems, and the mechanisms of protein synthesis inhibition involved in different catabolic conditions have been partially clarified. Moreover, recent studies have shown that cytokines can directly influence skeletal muscle contractility independent of changes in muscle protein content. Even though several gaps remain in our understanding, these observations may be useful in the development of strategies to control protein metabolism and muscle function in different clinical conditions.