Homocysteine (Hcy) is a sulfhydryl-containing amino acid, which is not acquired through the diet, but rather synthesized as an intermediate metabolite in the methionine cycle. Hcy is present in plasma, with normal levels between 5 and 15 mu mol/L, a slightly elevated level between 15 to 30 mu mol/L, moderate from 30 to 100 mu mol/L and a value > 100 mu mol/L classified as severe hyperhomocysteinemia (HHcy). HHcy has been associated with inflammation and atherosclerosis and is considered an independent risk factor for cardiovascular diseases (CVD). Here, we review the main evidence showing the association and the possible involvement of HHcy in the most common CVD.