Since time immemorial, women and men alike have undoubtedly recognized that pronounced changes periodically occur in the vasculature of the female reproductive tract. However, it was not until the beginning of the 20th century that it became clear these changes were under endocrine control by ovarian hormones. Within the last two decades, specific genes that regulate vascular growth and function have been identified (1), and we can now investigate their hormonal regulation. This is required to elucidate the physiological mechanisms that regulate changes in the endometrium throughout the menstrual cycle, the pronounced vascular changes that occur during implantation and placentation, and the pathophysiology of conditions such as dysfunctional uterine bleeding, uterine cancers, and endometriosis, which are major health problems in women. A key function of the vasculature is to provide a nutrient supply to the reproductive tract, and in most species three major types of regulation occur: vasodilation; changes in capillary permeability; and growth and development of new vessels. In virtually all species studied, estrogens produce dramatic increases in uterine blood flow caused by vasodilation, and in general uterine hyperemia (ie an increase in blood in the tissue) increases as the ratio of circulating estrogen/progesterone increases. Despite the fact that these dramatic changes in uterine hyperemia have been recognized for many years, the molecular mechanism (s) for this effect remain to be established and will not be further considered here.