The toll-like receptors (TLRs) are a family of microbe-sensing receptors on peripheral immune cells. TLRs have also been discovered to be present in the brain, particularly in circumventricular organs, microglia, and astrocytes. Some TLRs are strongly expressed in the embryonic brain and TLR3 and TLR8 have been implicated in neurogenesis and neurite outgrowth in the developing brain, whereas TLR2 and TLR4 have been shown to regulate adult neurogenesis. TLR2 and TLR4 also play a role in acute ischemic brain injury in the adult, although no neuroprotection was observed following perinatal hypoxic-ischemic injury. These findings suggest that different TLRs have specific roles in the immature and adult brain following brain damage.