This chapter discusses the clinical features, diagnosis, and management of HIV distal sensory polyneuropathy (DSP); toxic neuropathies, with emphasis on the antiretroviral (ARV)-associated neuropathies; and other neuropathies found in HIV-infected individuals. Subjects were classified as having asymptomatic DSP if they only had neurologic signs or as having symptomatic DSP if they also had paresthesias or pain in a study by Schifitto and coworkers. The study showed that use of these drugs was not a significant risk factor for incident symptomatic DSP. Such an effect may be related to preservation of immune function, forestalling the potential occurrence of neurotoxicity. This study also addressed the important issue of whether the presence of asymptomatic DSP is a risk factor for incident symptomatic DSP. Thus, it is not surprising that patients with advanced HIV infection and severe immunosuppression remain at the greatest risk of neurotoxicity due to ARV agents. The incidence, severity, progression, and reversibility of peripheral neuropathy from zalcitabine (ddC), as with other toxic neuropathies, are dose dependent. Unlike other toxic neuropathies, dapsone-induced peripheral neuropathy involves primarily motor nerves. Mononeuropathy multiplex (MM) is an infrequent manifestation of HIV infection. A reduced number of oxytocin neurons in the paraventricular nucleus of the hypothalamus have also been described, although the clinical significance of this is unclear. It has been suggested that the pathophysiological mechanism may be due to HIV infection itself as well as an autoimmune mechanism. It may arise from HIV itself or from medications used to treat HIV infection and other concomitant infections.