Over the last decade, substantial effort has been directed towards developing an insulin sensitising anti-inflammatory drug. This work has been inspired by the strong association between inflammation and obesity/insulin resistance, and mouse studies that show anti-inflammatory interventions improve insulin action. However, there is no convincing evidence that immune processes contribute substantively to the pathogenesis of insulin resistance in human obesity. Have we been swindled by the basic science? In this seminar, reasons for this translational roadblock will be explored and directions for future research suggested.