Dementia secondary to infectious disease, setting aside cases of transmissible spongiform encephalopathy (see Chapter 17) and the cognitive–motor abnormalities frequently associated with acquired immunodeficiency syndrome (AIDS), is distinctly unusual. Infectious disease as the primary cause of a dementing illness is usually a diagnosis of exclusion; lumbar puncture is often carried out in the clinical work-up of a demented patient – especially if the decline in mental status is rapidly progressive – in order to safely rule out a treatable infection (e.g. cryptococcal meningitis), unusual though this is, as the cause for a given individual's cognitive and neuropsychiatric decline. In a large experience of biopsies (approximately 5–10 per year) and autopsies (40–50 annually) carried out to establish the cause for dementia, we have rarely encountered – usually as a surprise finding – evidence of a central nervous system (CNS) inflammatory or infectious disease as the primary etiology. Such cases are, however, intriguing insofar as modern diagnostic tools can often establish an aetiological agent for the infection even when the only histopathological evidence for its existence (at autopsy) is widespread chronic inflammation of the brain and its overlying leptomeninges. Throughout the 1980s and 1990s, the range of known viruses and bacteria that target the CNS has widened substantially (Kennedy, 1990; Vinters et al., 1998). The availability of highly sensitive molecular diagnostic tests (especially the polymerase chain reaction, PCR), by which faint traces of molecular ‘footprints’ of bacterial or viral pathogens may be detected within neural tissue, allows the safe prediction that many new associations between micro-organisms and CNS/PNS disease will be made in the coming years (Darnell, 1993; Tompkins, 1992).