The brain remains a major target for HIV infection and a site of potential complications for HIV-infected individuals. Emerging data presented at the 2016 Conference on Retroviruses and Opportunistic Infections suggest that during the early stages of infection, activated CD4+ cells may traffic the virus into the central nervous system (CNS). HIV is detectable in cells and tissues of the CNS in some individuals despite suppressive antiretroviral treatment. A potential source of cerebrospinal fluid HIV escape may be compartmentalized HIV replication within macrophage lineage cells. Virally infected cells can traffic out of the CNS and may have the potential to reseed the systemic compartment. Additional modifiers of HIV-associated neurocognitive disorder (HAND) were identified, including female sex and hepatic dysfunction. Large epidemiologic studies reported an elevated risk of stroke among HIV-infected individuals, related to traditional vascular risk factors, history of recreational drug use, and HIV measures (lower CD4+ cell nadir and higher viral load). Brain imaging may provide a noninvasive means for detecting early changes in the brain associated with HIV infection and may assist in prognosis of HAND. Some potential adjunctive therapies to standard antiretroviral therapy for HIV-infected individuals were considered.