It has long been recognized that skeletal muscle can contain modest stores of triglyceride and that this depot of fuel can make a major contribution to energy production during exercise. More recently, an adverse effect of muscle triglyceride has begun to be defined within the context of insulin resistance. Animal and clinical investigations have revealed a significant relation between increased muscle triglyceride and insulin resistance, at least among mostly sedentary individuals. These observations have stimulated the development, or at least the refinement, of new methodologies to assess this aspect of 'regional' fat deposition. In parallel, there has also been important new work designed to enable better understanding of the factors that regulate muscle triglyceride and to determine whether fatty acids taken up by skeletal muscle are oxidized or stored, and how these pathways might be either altered by the presence of insulin resistance or, in turn, contribute to the pathogenesis of insulin resistance.