Duloxetine is a balanced serotonin noradrenaline re-uptake inhibitor that has recently become the first agent to receive regulatory approval for the treatment of painful diabetic neuropathy in the US. This compound has no other significant receptor or channel activities other than the serotonin and noradrenaline re-uptake inhibition mechanisms and works to diminish or control the symptoms of diabetic neuropathy. Duloxetine has no known neuroprotective or other effects that prevent the development of neuropathy in patients with diabetes. Its effectiveness in diabetic neuropathy confirms the proposed role of serotonin and noradrenaline as key mediators of the descending pain inhibition pathways of the brain stem and spinal cord. Clinical studies have demonstrated the high degree of safety and efficacy for the compound with no adverse effects on glycaemic control due to the action of duloxetine being identified.