SUMMARY
Brain HIV‐1‐infection may result in a syndrome of profound cognitive, behavioral and motor impairment known as AIDS dementia complex (ADC) in adults and HIV‐related encephalopathy in children. Although the introduction of highly active antiretroviral therapy (HAART) has prolonged and improved the lives of infected individuals, it is clear that HAART does not provide complete protection against neurological damage in HIV/AIDS. HIV‐1 associated dementia is a complex phenomenon, which could be the result of several mechanisms caused by those players using different intracellular signaling pathways. Understanding the causes of neurodegeneration during HIV‐1 infection and the factors which certain individuals develop disease can provide researches on new therapeutic targets to positively affect disease outcomes. Controlling CNS viral replication with HAART is an essential primary approach, but it should be complemented with adjunctive CNS‐directed therapeutics. Understanding the nature of HIV‐1 infection within the CNS as well as inflammatory responses will ultimately lead to the elimination of HIV‐associated neurocognitive disorders. Copyright © 2011 John Wiley & Sons, Ltd.