Recent in-vitro studies have improved our understanding of how bacteria interact with cerebral endothelial cells and cross the blood-brain barrier. Several animal studies using rat and rabbit models of bacterial meningitis have revealed mediators of inflammation that are believed to play a key role in secondary brain damage, including reactive oxygen species, nitric oxide, and excitatory amino acids. Treatment with free-radical scavengers, nitric oxide synthase inhibitors, excitatory amino acid antagonists, as well as the anti-inflammatory cytokine interleukin-10 was beneficial in experimental bacterial meningitis. Apart from dexamethasone these agents hold major promise for the adjunctive therapy of bacterial meningitis in clinical practice.