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NeuroAIDS is becoming a major health problem among AIDS patients and long-term HIV survivors. As per 2009 estimates of UNAIDS report, more than 34 million people have been infected with HIV out of which ≥ 50% show signs and symptoms of neuropsychiatric disorders. These disorders affect central nervous system (CNS) and peripheral nervous systems (PNS). CNS is one of the most protected organ systems in body which is protected by blood-brain barrier (BBB). Not only this, most of the cells of CNS are negative for receptors and co-receptors for HIV infections. Neurons have been found to be completely nonpermissive for HIV infection.These facts suggest that neurotoxicity could be an indirect mechanism responsible for neuropsychiatric complications. In this review, we will discuss the importance of different cell types of CNS and their contribution toward neurotoxicity.