Over the past 5 years it has become apparent that cytokines are produced by myocytes in the absence of any markers of inflammation. Specifically, the gene encoding for the cytokine interleukin (IL)-6 is present in skeletal muscle and is induced by muscle contraction and, in some circumstances by insulin. In turn, IL-6 protein is produced throughout the myocyte and released into the circulation where it acts in an "endocrine like" manner to activate processes designed to maintain metabolic homeostasis. Hence, it has become apparent that IL-6 may be a factor that is coupled to genes involved in metabolic processes both within skeletal muscle and adipose tissue. Relatively less is known regarding the upstream factors that induce the transcription of IL-6. However, it is clear that IL-6 production is activated by intracellular calcium levels, mitogen-activated protein kinases, reduced glycogen availability and other cytokines such as IL-1 beta. This review will briefly discuss the signaling pathways involved in IL-6 gene transcription.