While combination antiretroviral therapy (CART) has decreased the incidence of HIV-associated dementia, the severest form of HIV-associated neurocognitive disorders (HAND), mild neurocognitive disorder and asymptomatic neurocognitive impairment continue to persist, and there is evidence that neurocognitive deficits present even in acute HIV infection. Recent studies demonstrate that CART regimens with higher central nervous system (CNS) penetration effectiveness ranks may improve neurocognitive functioning. Considering these factors, earlier treatment initiation may be considered to protect the CNS. The functional impact of HAND on daily activities should be monitored. Areas that need further research are potential neurotoxicity of antiretrovirals, the eradication of potential latent reservoirs in the brain, when to start treatment to protect the CNS, and the neurological impact of HIV on the CNS in acute infection.