About 50% of patients with hepatitis C virus (HCV) infection complain of neuropsychiatric symptoms, "brain fog", weakness, fatigue, and exhibit some degree of quality of life impairment, irrespective of the severity of liver disease. Since the first observation of HCV-related cognitive deficits, 10 studies have been published that have evaluated neuropsychiatric performance in patients with HCV infection and different degrees of hepatic impairment. Unfortunately, these have often included patients with cirrhosis, patients who had acquired the infection through previous intravenous drug misuse, who had a history of relatively recent treatment with interferon, or were on psychoactive medication. In addition, different neuropsychological batteries and tests that explored different cognitive domains were used, which makes the results of the studies difficult to compare. Finally, limited information is available on the pathogenesis of HCV-related cognitive impairment. Cerebral and/or systemic inflammation may be important players but their potential role has not been substantiated by experimental data. The present review outlines the available evidence of the presence of cognitive impairment in patients with HCV infection, with a focus on the potential relationship with cerebral and/or systemic inflammation.