Summary. -Viral neuroinvasion via the olfactory system has been investigated in a variety of virus-animal models by scientists in many fi elds including virologists, pathologists, and neurologists. In humans, herpes simplex virus type 1 (HSV-1), human herpesvirus 6 (HHV-6), Borna disease virus, rabies virus, and infl uenza A virus have been shown to take the olfactory route for neuroinvasion based on forensic and post-mortem specimens. Th is article briefl y summarizes the anatomy, physiology, and immunology of the olfactory system and presents a battery of neurovirulent viruses that may threaten the human brain by invading through this peripheral pathway, especially focusing on two of the most intensively studied viruses -HSV-1 and infl uenza A virus. Viruses may insidiously invade the olfactory neural network not only to precipitate encephalitis/encephalopathy but also to promote the development of neurodegenerative and demyelinating disorders. Substantial information obtained by analyzing human specimens is required to argue for or against this hypothesis.Keywords: virus; olfactory neuron; human brain; encephalitis; neurodegenerative disorders Acta virologica 59: 338 -349, 2015 doi:10.4149/av_2015_04_338 E-mail: mori@shubun-ac.jp; phone: +81-586-45-2101 Abbreviations: CNS = central nervous system; CSF = cerebrospinal fl uid; HHV-6 = human herpesvirus 6; HPAI = highly pathogenic avian infl uenza; HSE = herpes simplex encephalitis; HSV-1 = herpes simplex virus type 1; IFN = interferon; ORNs = olfactory receptor neurons; RIG-1 = retinoic acid inducible gene 1; TLR3 = toll-like receptor 3