Despite effective antimicrobial therapy, mortality and morbidity from bacterial meningitis remain unacceptably high. Meningitis deaths occur as a consequence of intracranial and systemic complications. The neurologic and otologic sequelae reflect structural injury to brain and cochlear tissues. Over the past decade, experimental studies have demonstrated that meningitis-related vascular and cortical injury is largely caused by the massive neutrophilic inflammatory reaction, whereas hippocampal and cochlear injury is driven by both the host response and bacterial toxins. The benefit of adjunctive corticosteroid therapy proves the principle that the key to improve clinical outcome is combining antibiotics with drugs directed against pathophysiologically relevant targets; its limitations in efficacy and applicability highlight the need for novel adjunctive therapies. Promising targets were identified recently through animal studies, and include limiting the release of toxic bacterial products (by using nonbacteriolytic antibiotics) and interfering with the generation of host-derived cytotoxins (by using neutrophil apoptosis-inducing agents).