The pathogenesis of liver damage associated with the chronic hepatitis C virus (HCV) infection is largely immunomediated. However, some frequent histopathological features, such as fatty liver, suggest a direct cytopathic effect of HCV. The direct responsibility of HCV in the pathogenesis of steatosis is shown by: (1) the association with HCV genotype 3 infection, suggesting that some viral sequences are involved in the intracellular accumulation of triglycerides; (2) the correlation between the severity of steatosis and HCV replication levels; and (3) the association between the response to antivirals and the disappearance of steatosis. Experimental studies have shown that the core protein of HCV is capable and sufficient to induce a triglyceride accumulation in hepatocytes. Moreover, the observation that chronic hepatitis C patients have reduced serum levels of apolipoprotein B suggests an interference with the very-low-density lipoprotein assembly. In patients with a sustained virological response induced by antiviral therapy, such levels are normalized. Other observations suggest that HCV may increase neolipogenesis and inhibit fatty acid degradation in mitochondria. Put together, all of these mechanisms contribute to the pathogenesis of fatty liver frequently observed in hepatitis C.