The hepatitis C virus (HCV) is a common blood-borne illness that affects up to 2% of the world's population and almost 4 million Americans. Cognitive impairment, or difficulty with thinking, has become a well-established symptom in persons with end stage liver disease. It was previously assumed that cognitive impairment was a consequence of cirrhosis-associated hepatic encephalopathy. Recent evidence, however, suggests that approximately one-third of people with chronic HCV experience cognitive impairment even in the absence of cirrhosis and that its occurrence is unrelated to other indices of liver function, such as laboratory values, viral load, and genotype. In the present review, evidence outlining the presence of cognitive deficits associated with HCV, possible etiological factors, effects of antiviral therapy, and co-infection with human immunodeficiency virus (HIV) is presented. Implications of these findings and directions for future work are discussed.