Bacterial infection of human vasculature can lead to unregulated systemic activation of coagulation and innate immunity and rapidly becomes life threatening. Neisseria meningitidis is a vascular pathogen that causes fatal septic shock and meningitis. Post-mortem histological analysis of tissues from individuals infected with N. meningitidis show large bacterial aggregates in close association with the vascular wall of small vessels. The ability of this bacterium to colonize blood vessel endothelium is likely to impact its capacity to both multiply in the blood stream and reach the brain. This process is referred to as vascular colonization. Recent work from our group exploring the early steps in N. meningitidis vascular colonization will be reported, from attachment to proliferation and dissemination, focusing on the bacterial–host interaction.