The increasing number of females participating in physical activity has heightened our awareness of changes in the menstrual cycle which often accompany physical activity. As such, there has been a considerable amount of research investigating the relationships between menstrual cycle changes and bone mineral density, performance, ventilation and substrate metabolism. A number of researchers have concluded that there may be enhanced fat metabolism in eumenorrhoeic versus amenorrhoeic females, or in the follicular phase versus the luteal phase of the menstrual cycle, due to the theoretical estrogen level in eumenorrhoeic versus amenorrhoeic females or the luteal phase versus the follicular phase. However, a definite relationship between resting estrogen level and substrate metabolism has not been clearly established. In addition, the mechanisms which may be responsible for the effect of estrogen on substrate metabolism have not been addressed. It appears that the effects of estrogen on metabolism may be via the effect of estrogen on glucogenic hormones or lipolytic enzymes. Therefore, the primary purpose of this review is to explore the effects of estrogen on substrate metabolism. Menstrual cycle physiology and possible mechanisms for the effects of estrogen on metabolism, as well as previous research on estrogen and metabolism in rats and humans, will be discussed.