Thrombus formation and vasospasm are involved in the initiation of acute ischemic events in the heart. Gender differences in persons with coronary artery disease and the incidence of myocardial ischemia have been clearly documented. In addition, it is well established that sex hormones influence the risk of developing coronary artery disease. Epidemiologic studies suggest that estrogen may exert a protective effect, yet the results of recently completed and ongoing prospective trials of estrogen and hormone (estrogen + progesterone) replacement suggest that these hormones can increase thrombotic events in postmenopausal women. This review focuses on sex (gender) differences in hemostasis and vascular reactivity and on the influence that sex hormones have on these physiologic systems. This review takes the novel approach of focusing on sex differences in hemostasis and vascular reactivity in healthy premenopausal women and men of a similar age. By comparing men and women in this age group, the confounding issues of age, pathology, or decline in sex hormone levels are avoided. Animal and in vitro investigations pertinent to examining potential cellular mechanism(s) of sex hormones in mediating these sex differences are discussed. We assume there is a relationship between the normal physiologic and pathologic effects of sex hormones; elucidating sex differences in normal cardiovascular function will help clarify the basis for sex differences in the incidence and manifestations of coronary heart disease and will aid in the future development of gender-specific therapies for cardiovascular disease.