With the discovery of a number of immunomodulatory cytokines 15 to 20 years ago [1, 2] came the observation that so-called “inflammatory cytokines” such as TNFα, IL-6, IL-1α and IL-1β were capable of exerting effects on the body’s major metabolic tissues: skeletal muscle, adipose tissue and the liver [3]. These cytokines normally circulate in low concentrations and are expressed in a wide variety of tissues, including those mentioned above. Since these cytokines often appear to be elevated in various disease states, such as cachexia [4], Type 1 [5] and Type 2 [6] diabetes, the hypothesis that these cytokines may be involved in the aetiology of these diseases has been the subject of numerous investigations. Much work has focused on the role of TNFα in the induction of Type 2 diabetes and insulin resistance, and although somewhat controversial, it is generally accepted that TNFα has a role to play in the aetiology of insulin resistance [7]. However, because IL-6 is often, but somewhat incorrectly [8], grouped together with TNFα as the so-called “pro-inflammatory” cytokines, IL-6 is seen as having a similar role to TNFα in terms of metabolism. It is true that many studies suggest that both IL-6 and TNFα have similar functions, but there are also quite a number that make observations to the contrary (for review see [9]). While some studies have shown a link between IL-6 and impaired insulin action, there is a strong body of literature suggesting that IL-6 does not cause insulin resistance, and in some instances may have beneficial effects on this disease. This review attempts to summarise the roles of IL-6 in insulin action, and show that IL-6 may induce insulin resistance in certain instances, but not in others.