Neisseria meningitidis is an extracellular pathogen, which, once in the bloodstream, has the ability to form microcolonies on the apical surface of endothelia. Pathogen interaction with microvessels is mediated by bacterial type IV pili and two receptors on endothelial cells: CD147 and the β2-adrenoceptor. CD147 facilitates the adhesion of diplococci to the endothelium, whereas the β2-adrenoceptor facilitates cell signaling, and crossing of the blood–brain barrier. In this review, we discuss how meningococcal interaction with endothelial cells is responsible for the specific clinical features of invasive meningococcal infection such as meningitis, and a peripheral thrombotic/vascular leakage syndrome possibly leading to purpura fulminans.