Hepatitis C virus (HCV)-associated nervous system disorders have been described with increasing frequency in the literature, but definitive conclusions regarding their pathogenesis is for the most part lacking. Best established are complications due to cryoglobulinemia, vasculitis, and thrombosis, in which focal disturbances of peripheral nerve or brain function are seen. Rarer are cases of inflammatory encephalitis and/or myelitis similar to other flaviviral infections. A body of literature detailing cognitive abnormalities is accumulating; still unclear is whether these neuropsychologic effects are due specifically to HCV or to other processes associated with HCV infection. HCV has been localized to the central nervous system; much of its basic neurobiology remains to be described and awaits further correlation with clinical abnormalities.