The recent discovery of the family of Toll-like receptors has vastly expanded our understanding of the mechanisms by which the innate immune system recognizes and responds to a wide variety of microbial and endogenous pathogens. Toll-like receptors are transmembrane proteins that upon ligation with their cognate ligands trigger the production of cytokines, enzymes and other inflammatory agents. In the CNS Toll-like receptors are expressed predominantly by glial cells. In particular, the vastly abundant astrocytes are likely to be the major contributors to inflammatory responses within the CNS. Studies of the murine brain abscess model revealed that Toll-like receptor 2 plays a pivotal role in the generation of immune responses to Staphylococcus aureus. Although Toll-like receptor signaling is essential in antimicrobial defense, it may also lead to bystander injury of CNS tissue.