Bacterial meningitis is among the top ten causes of infectious disease-related deaths worldwide, with up to half of the survivors left with permanent neurological sequelae. The blood-brain barrier (BBB), composed mainly of specialized brain microvascular endothelial cells, maintains biochemical homeostasis in the CNS by regulating the passage of nutrients, molecules and cells from the blood to the brain. Despite its highly restrictive nature, certain bacterial pathogens are able to gain entry into the CNS resulting in serious disease. In recent years, important advances have been made in understanding the molecular and cellular events that are involved in the development of bacterial meningitis. In this review, we summarize the progress made in elucidating the molecular mechanisms of bacterial BBB-crossing, highlighting common themes of host-pathogen interaction, and the potential role of the BBB in innate defense during infection.