Distal sensory polyneuropathy (DSP) is the most common neurologic complication of HIV infection and a major cause of morbidity in HIV-infected patients. DSP may occur secondary to HIV (HIV-DSP) or be due to antiretroviral drug toxicity. Timely detection of the symptoms and signs of DSP in patients who have HIV may allow for the reversal of the toxic effects of antiretrovirals and for the initiation of symptomatic treatment. The pathogenic mechanism of HIV-DSP is likely multifactorial. Restorative therapies for DSP are not currently available but recent advances have led to novel symptomatic therapies. This article highlights the risk factors, pathogenesis, pathology, clinical features, diagnostic studies, differential diagnosis, and treatment of HIV-associated neuropathy.