HIV-1 infects the central nervous system (CNS) and it has been feared that the CNS may be a sanctuary site where HIV-1 could hide and continue to replicate despite otherwise effective antiretroviral treatment. Neurological HIV-1 related symptoms, cerebrospinal fluid (CSF) viral load, intrathecal immunoactivation and CSF drug concentration measurements are considered in this review of antiretroviral treatment effects on CNS HIV-1 infection. We conclude that antiretroviral combination treatment regimens improve neurocognitive symptoms in HIV-1 infection and substantially lower CSF viral load. The threat of an increasing number of patients with neurological symptoms and continued HIV-1 replication in the brain despite otherwise effective antiretroviral therapy has not yet proved to be a problem. It is, however, important to keep this potential risk in mind, and more longitudinal prospective studies addressing the issue of antiretroviral treatment effects on CNS HIV-1 infection are needed.