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Advances in the pathophysiology and treatment of diabetic peripheral neuropathy. Diabetic peripheral neuropathy (DPN) is a common, debilitating disorder that results in sensory loss, gait dysfunction, propensity to skin ulceration that can lead to limb amputations, and neuropathic pain. DPN has a negative impact on patients' mood and quality of life and is also associated with increased mortality. Disappointingly, aggressive treatment of hyperglycemia does not adequately prevent DPN, particularly in patients with type 2 diabetes, and new, more effective treatments for DPN are urgently needed. Recent decades have witnessed a growing understanding of the risk factors and molecular mechanisms of DPN, such as the importance of axoglial interactions and metabolic derangements beyond hyperglycemia. Despite expanding knowledge, the translation of preclinical insights to treatments that benefit patients remains challenging. This review will cover DPN epidemiology and risk factors, including social determinants of health, DPN pathophysiology and genetics, currently recommended diagnostic and treatment approaches, and available clinical outcomes assessments and biomarkers. Discussion of each of these topics will emphasize recent advances in the field and focus on the challenges and necessary new directions in DPN research.