NeuroAIDS is one of the main complications of chronic HIV-infection. The Central Nervous System is an immunologic sanctuary for HIV and allows the persistence of the virus despite an efficient antiretroviral therapy. HIV-1 could promote the neurodegeneration through the induction of inflammation by the release of neurotoxins from infected cells. In addition, several viral proteins can directly contribute to the neuronal damages, activate cell-signaling involved in the control of cellular survival and apoptosis, favoring functional alterations in the target cells. Macrophages play a key role in the pathogenesis of NeuroAIDS, they are the main reservoirs of the infection in brain, promoting the inflammatory escalation, astrogliosis and degeneration process. This review aims to highlight the virological aspects associated with NeuroAIDS including pathogenesis, and treatment of HIV-1 in the CNS sanctuaries.