HIV associated neurocognitive disorders and their histopathological correlates largely depend on the continuous seeding of the central nervous system with immune activated leukocytes, mainly monocytes/macrophages from the periphery. The blood-brain-barrier plays a critical role in this never stopping neuroinvasion, although it appears unaltered until the late stage of HIV encephalitis. HIV flux that moves toward the brain thus relies on hijacking and exacerbating the physiological mechanisms that govern blood brain barrier crossing rather than barrier disruption. This review will summarize the recent data describing neuroinvasion by HIV with a focus on the molecular mechanisms involved.