The blood-cerebrospinal fluid barrier physiologically protects the meningeal spaces from blood-borne bacterial pathogens, due to the existence of specialized junctional interendothelial complexes. Few bacterial pathogens are able to reach the subarachnoidal space and among those, Neisseria meningitidis is the one that achieves this task the most constantly when present in the bloodstream. Meningeal invasion is a consequence of a tight interaction of meningococci with brain endothelial cells. This interaction, mediated by the type IV pili, is responsible for the formation of microcolonies on the apical surface of the cells. This interaction is followed by the activation of signaling pathways in the host cells leading to the formation of endothelial docking structures resembling those elicited by the interaction of leukocytes with endothelial cells during extravasation. The consequence of these bacterial-induced signaling events is the recruitment of intercellular junction components in the docking structure and the subsequent opening of the intercellular junctions.