The most common cause of death for older American women is cardiovascular disease. Before menopause, women are protected against cardiovascular disease by an estrogen-dominant milieu. This is evidenced by a favorable lipoprotein profile. After menopause the circulating lipoproteins move toward a more atherogenic profile. Estrogen replacement therapy in the postmenopausal years is associated with a 50|X% (ever-users) to 70|X% (current users) reduction in the risk of coronary heart disease and stroke. The mechanism for this protection against cardiovascular disease by estrogen is partly through a beneficial impact on the lipoprotein profile and partly through a direct effect on arterial vessels. The addition of a progestational agent to an estrogen replacement program is necessary to prevent endometrial cancer. A contemporary method of hormone replacement uses a daily combination of estrogen with a small dose of progestin. This method improves compliance by avoiding withdrawal bleeding. Evidence is accumulating that this small progestational dose can protect the endometrium and avoid a significant negative impact on lipids and the lipoprotein profile.