In the postmenopausal period, cardiovascular diseases are a frequent chronic condition leading to high risk of myocardial infarction and death. Recently hyperhomocysteinemia and even mildly elevated plasma concentrations of homocysteine have been recognized as independent risk factors for vascular damage predisposing to arteriosclerosis. Elevated plasma levels of homocysteine induce vascular endothelial damage and are frequently associated with low folate levels. In this review we evaluate literature data on some aspects related to menopause and homocysteine metabolism. In particular, we show the effect of folic acid supplementation on homocysteine concentrations and on homocysteine-related thiols, such as cysteine and cysteine-glycine, as well as the relationship with glucose, insulin, and lipidic metabolism in postmenopausal women. We also analyze the influence of folate supplementation on endothelial function, by brachial artery flow-mediated dilatation (endothelium-dependent) and nitroglycerine-induced dilatation (endothelium-independent) before and after a methionine load. Folate administration in postmenopausal women is able to reduce high plasma homocysteine levels and to modify impaired endothelial function induced by hyperhomocysteinemia.