Both diabetes and chronic hepatitis C virus (HCV) infection are common conditions that often coexist in the same subject. Studies seem to confirm the presence of an association between them. Mechanisms leading to HCV-induced insulin resistance and glucose intolerance are beginning to be elucidated. Insulin resistance in the setting of chronic HCV infection could be related etiologically to viral factors but is also often seen with concomitant nonalcoholic fatty liver disease, the hepatic manifestation of the metabolic syndrome. Insulin resistance decreases the likelihood of response to interferon-based therapies and may be an independent risk factor for the progression of HCV-related liver disease.