In developed countries the effect of highly active antiretroviral therapy (HAART) on the neurological complications in the short term has been well described, but the long-term effects are only just starting to be clarified. These issues are best discussed within a framework that structures the complications according to whether they are direct or indirect. Within this framework this chapter deals briefly with the more significant aspects of nervous system involvement in HIV infection emphasizing three points: possible new complications in developing countries, new complications in HAART-treated patients as well as complications such as progressive multifocal leukoencephalopathy (PML) that have only marginally changed with HAART, and future directions. The direct complications such as dementia and neuropathy are organized according to the degree of advancement of HIV disease and anatomical region involved. With the introduction of HAART, some aspects of investigations have changed; however, this is an evolving area that still needs clarification. There are several myopathies that have been linked to HIV disease. The association seems to be at least in part causal rather than just associative. The two most important are polymyositis and inclusion body myositis. The indirect neurological complications related to HIV disease are many. Only the more important are discussed in the chapter. The most significant aspects of these disorders in the era of HAART are that the incidence of opportunistic infections has significantly declined with HAART and that HAART may induce the clinical expression of previously subclinical disease through the immune reconstitution syndrome.