Diabetes mellitus targets the peripheral nervous system in unique but disabling ways. Although several mechanisms may target peripheral neurons, they render a degenerative pattern of damage that begins in distal terminals. Moreover, sensory neurons are involved early, motor neurons later. By studying a variety of diabetic neuropathy models in rats, mice, and other species, an overall appreciation of its neurodegeneration emerges. Understanding how mechanisms of diabetes complications target peripheral neurons selectively may offer opportunities to intervene before irretrievable neuron loss develops.