Members of the toll-like receptor (TLR) family are pathogen recognition receptors that recognize pathogen-associated molecular patterns. TLRs mediate the modulation of innate immune responses and influence the development of adaptive immunity. TLR3 is the first identified antiviral TLR that recognizes dsRNA. TLR3 plays a central role in the activation of host immune responses to viral infections and shows detrimental or protective effects against various viral infections. Several viruses are neurotropic and can infect the central nervous system, leading to neuropathologies such as encephalitis, encephalopathy, meningitis, and neuritis. Single nucleotide polymorphism (SNP) in the TLR3 gene is associated with the susceptibility to a spectrum of nervous system viral infections. In this review, we discussed the existing knowledge of TLR3 immune responses on the basis of the experimental evidence and coherent picture of the SNP in TLR3 that is associated with various neurotropic virus infections.