The central nervous system (CNS) and the immune system are considered major target organs for HIV infection. The neurological manifestations directly related to HIV are acute viral meningitis, chronic meningitis, HIV associated dementia, vacuolar myelopathy and involvement of the peripheral nervous system. Changes in diagnosis and clinical management have changed the aspect of HIV infection so that it is no longer a fatal disease, and has become a chronic disease requiring sustained medical management. After HAART the incidence of most opportunistic infections, including those affecting the CNS, has dropped markedly. Some studies suggest that neurological involvement of infected patient occur with different frequency, depending on HIV subtype involved in the infection. Subtype C may have reduced neuroinvasive capacity, possibly due to its different primary conformation of HIV transactivating regulatory protein (Tat), involved in monocyte chemotaxis. This review focus on physiopathologic aspects of HIV infection in CNS and its correlation with HIV clades.