Menopause is not a disease, but a physiologic phase of a woman's life, due to the changes of their hormonal status. Fastidious symptoms may be associated with changes in the metabolism together with new cardiovascular risk factors, particularly aggressive for the female cardiovascular system, unprepared because of the protection due to the fertile period. Changes of the lipid profile, obesity, hypertension, glucose intolerance and diabetes mellitus may intervene as severe risk factors. Cardiovascular disease represents therefore the most frequent cause of mortality and morbidity also in the female gender more than cancer either in the United States as in Europe. The risks related to post-menopause are mainly due to the abrupt interruption of estrogen, which has indirect protective effects on lipid, glycidic metabolism and direct effects on vessel function. They have, in fact, vasodilator action due to nitric oxide release, calcium-antagonist like action and an antiproliferative effect on smooth muscle cells. Post-menopause is also frequently associated with hypertension, the most frequent related factor to coronary artery disease. Hypertension is due to increased body mass index, with insulin-resistance, sodium retention, increased blood viscosity and estrogen deficiency with increased smooth muscle cell proliferation which determines an increase in systemic vascular resistance. Age and estrogen deficiency are together the most important cause of cardiovascular risk in post-menopause. The discovery of alpha and recently beta estrogen receptors on coronary female vessels unaffected by atherosclerosis either during pre and post-menopause phase are possible key of interpretation of pathophysiology of coronary artery disease in women, with important therapeutic consequence.