Derangements in whole body glucose and lipid metabolism, accompanied by insulin resistance, are key features of obesity and the metabolic syndrome. A role for inflammation as a causative factor is an emerging concept in the field of metabolic disease. Research has centred on identifying important inflammatory markers, and tumour necrosis factor-alpha has been highlighted as a key mediator of insulin resistance, as well as interleukin-6 (IL-6). A parallel ongoing endeavour is the unravelling of molecular mechanisms underlying the beneficial effects of physical exercise on whole body glucose and lipid metabolism. Release of IL-6 from the contracting skeletal muscle has been proposed to be one of the molecular signals promoting the beneficial exercise-induced effects. These two opposing views of IL-6 underscore that the role of IL-6 in whole body physiology is incompletely resolved. This review aims at summarizing the current data on mechanisms by which IL-6 may impact on glucose and lipid metabolism.