The choroid plexus is an endothelial–epithelial vascular convolute that, besides producing the cerebrospinal fluid, is the location of the inner blood–cerebrospinal fluid barrier. This latter property offers central nervous system-invading bacteria the opportunity to target the choroid plexus as an entry gate for crossing into the brain, leading to inflammatory consequences as meningitis. During this process, the bacteria will engage with endothelial cells first, and, after leaving the blood vessels, with the epithelium that provides the barrier function at the choroid plexus. Interactions of bacterial virulence factors with endothelial and epithelial surface proteins as well as activated host cell signaling pathways are involved during overcoming of the barrier. The host cells at the choroid plexus respond to the challenge by staging an inflammatory response and recruiting immune cells. In this chapter, we summarize the known events taking place at the choroid plexus during infection with bacteria and discuss further aspects that might be of significant interest, as endothelial/epithelial interplay as well as impact of the gut microbiota via the gut–brain axis.