The explosion of the toll-like receptors (TLRs) over the past decade has touched almost every field of mammalian biology and neuroscience is not an exception. The current advent of research papers examining the TLRs in the central nervous system (CNS) signifies that these receptors are not only involved in peripheral innate immunity but may also play a role in the development and regulation of CNS inflammation, neurodegeneration and brain trauma. This review addresses the potential role of TLRs in the brain and how they may be involved in various neuropathologies.