Inflammation is emerging as a critical mechanism underlying neurological disorders of various etiologies, yet its role in altering brain function as a consequence of neuroinfectious disease remains unclear. Although acute alterations in mental status due to inflammation are a hallmark of central nervous system (CNS) infections with neurotropic pathogens, post-infectious neurologic dysfunction has traditionally been attributed to irreversible damage caused by the pathogens themselves. More recently, studies indicate that pathogen eradication within the CNS may require immune responses that interfere with neural cell function and communication without affecting their survival. In this Review we explore inflammatory processes underlying neurological impairments caused by CNS infection and discuss their potential links to established mechanisms of psychiatric and neurodegenerative diseases.