Homocysteine, a sulfuric amino acid involved in methionine metabolism, belongs to the group of intracellular thiols. Hyperhomocysteinemia is frequent in the Caucasian and its role in vascular pathology has been clearly established. In hepatology, experimental data in transgenic mice deficient in homocysteine metabolism enzymes have shown the presence of severe liver steatosis with occasional steatohepatitis. In chronic hepatitis C, preliminary data have shown that hyperhomocysteinemia is an independent risk factor for steatosis or even fibrosis. The physiopathological mechanism has now begun to be better understood. On one hand, there is a strong correlation between homocysteine and insulin resistance whatever its etiology. On the other hand, homocysteine has a direct effect on the liver, resulting in overexpression of SREBP-1 and favoring steatosis. It stimulates proinflammatory cytokine secretion such as NF kappa B increasing the risk of NASH. Finally, homocysteine could increase the risk of fibrosis by stimulating TIMP 1. Moreover, hepatitis C virus induces hypomethylation of STAT 1 and could decrease the antiviral activity of interferon. Results from in vitro studies have shown that the normalization of STAT 1 methylation by bringing betaine and S Adenosyl Methionine (which belongs to homocysteine cycle) restores the antiviral activity of interferon. Finally, treatment of hyperhomocysteinemia could have favorable consequences in steatohepatites and HCV infection [75, 76] .