Far from being an immune-inert site, the cells of the CNS, including microglia, astrocytes and neurons, express an abundance of innate immune receptors, including toll like receptors (TLR), which recognize conserved structural motifs in pathogens. These TLRs have been implicated in both infectious and non-infectious CNS pathology and appear to play important roles in both tissue surveying and repair. Therapeutics that modulate their activity are being explored for the treatment of infectious and inflammatory diseases.