The metabolic syndrome and the hepatitis C virus (HCV) infection are 2 global health care challenges with a complex interaction. Insulin resistance, a central component of the metabolic syndrome, is epidemiologically and pathophysiologically intrinsically linked to HCV infection. Insulin resistance and diabetes affect clinical outcomes in patients with liver disease related to HCV, namely, incidence of hepatocellular carcinoma, liver-related mortality, fibrosis progression rate, response to antiviral therapy, and possibly the incidence of cardiovascular events. Viral and metabolic steatosis and its interactions with HCV and the metabolic syndrome are discussed. Management and the need for further research conclude the article.