The most recent (2011) National Diabetes Fact Sheet states the combined diagnosed and undiagnosed number of diabetes cases in the United States is approaching 25 million, and another 79 million are prediabetic. Of the diabetes patients, 60-70% suffer from mild to severe neuropathy. This combined loss of sensory and motor control in diabetic limbs is usually considered an irreversible, progressive process. Patients suffering from these losses are at a significantly higher risk for development of foot ulceration, frequently leading to infection and partial or major limb amputation. However, a review of focal nerve entrapment surgical decompression literature suggests that several diabetic sensorimotor polyneuropathy (DSPN) symptoms and complications are potentially partially reversible or preventable. Decompression surgery represents a paradigm shift in treatment protocols because it both relieves pain and restores protective sensation, while providing significant protection against a cascade of serious foot complications. This review surveys current research regarding the biological basis for diabetic focal entrapment neuropathy. Metabolic dysfunction related to aldose reductase, oxidative stress, and advanced glycation end products are considered and correlated to peripheral nerve enlargement and entrapment. In addition, observational studies correlated to that biological basis are presented as well as surgical outcomes illustrating the effect of decompression on DSPN symptomatic relief, nerve function, and protection against complications.