The paradigm that dysfunctional mitochondrial bioenergetics is central to the pathogenesis of diabetes complications is widely held, though the specific molecular events by which these metabolic defects lead to structural pathology remains largely undefined. In the kidney, several defects localised to mitochondria have been shown. Lesions are commonly observed at the level of the electron transport chain, where substrate utilisation and energy production are regulated. However, other deficiencies have been demonstrated, including aberrant mitochondrial networking and biogenesis, altered mitophagy and increased susceptibility to mitochondrial permeability transition. Novel mitochondria-targeted compounds are urgently required to test the therapeutic potential of restoring mitochondrial homeostasis at sites of diabetic complications. It is hoped that as the molecular events that drive mitochondrial form and function are elucidated, new targets of therapy will be revealed, which will ultimately reduce the progression to end-organ injury in patients with diabetes.