Diabetic neuropathy (DN) is the most common complication of diabetes mellitus, and it imposes a considerable burden on a patient's quality of life and the health-care system. Despite the prevalence and severity of DN, there are no effective treatments. Pathogenetic evidence suggests that DN is marked by degeneration of dorsal root ganglion (DRG) neurons in peripheral nerves, and that DRG mitochondria are particularly affected. DRG mitochondria are especially vulnerable because they are the origin of reactive oxygen species production in the hyperglycemic neuron. Accumulating evidence indicates that neuronal mitochondria are subject to damage at the level of their DNA, and their outer and inner membranes, and also via deregulation of mitochondrial fission and fusion proteins that control mitochondrial shape and number. This Review will survey the mechanisms of mitochondrial degeneration in the pathogenesis of DN, highlighting potential mitochondrial sites for therapeutic intervention.