HIV/SIV invade the central nervous system, causing severe nerve pathological changes and AIDS related neural cognitive dysfunction(HAND). While effectively combined with highly active antiretroviral therapy, the incidence of HAND in the infected is still high. It is universally accepted that HIV/SIV could penetrate BBB(blood brain barrier) invading CNS in the early stage of infection through infecting brain capillary endothelial cells or just destroying the tight junction between the endothelial cells(ECs), however the mechanism of HIV/SIV invading BBB is unclear. There are several more renowned hypotheses towards HIV/SIV invading CNS, including virus directly infecting ECs hypothesis, monocyte/macrophage invasion hypothesis, T cells induced penetrating BBB hypothesis, and the hypothesis of liquid phase into ECs. This article will elucidate molecular mechanisms of HIV/SIV invading BBB.