Human immunodeficiency virus (HIV) is a neurotropic virus that enters the central nervous system (CNS) early in the course of infection. Although highly active antiretroviral therapy (HAART) has resulted in remarkable decline in the morbidity and mortality in AIDS patients, controlling HIV infections still remains a global health priority. HIV access to the CNS serves as the natural viral preserve because most antiretroviral (ARV) drugs possess inadequate or zero delivery across the brain barriers. The structure of the blood–brain barrier (BBB), the presence of efflux pumps, and the expression of metabolic enzymes pose hurdles for ARV drug-brain entry. Thus, development of target-specific, effective, safe, and controllable drug delivery approach is an important health priority for global elimination of AIDS progression. Nanoformulations can circumvent the BBB to improve CNS-directed drug delivery by affecting such pumps and enzymes. Alternatively, they can be optimized to affect their size, shape, and protein and lipid coatings to facilitate drug uptake, release, and ingress across the barrier. Improved drug delivery to the CNS would affect pharmacokinetic and drug biodistribution properties. This review focuses on how nanotechnology can serve to improve the delivery of antiretroviral medicines, termed NanoART, across the BBB and affect the biodistribution and clinical benefit for NeuroAIDS.