Neisseria meningitidis is responsible for two major diseases: cerebrospinal meningitis and/or septicemia. The latter can lead to a purpura fulminans, an often-fatal condition owing to the associated septic shock. These two clinical aspects of the meningococcal infection are consequences of a tight interaction of meningococci with host 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 a microbiological synapse. A low level of bacteremia is likely to favor the colonization of brain vessels, leading to bacterial meningitis, whereas the colonization of a large number of vessels by a high number of bacteria is responsible for one of the most severe forms of septic shock observed.