Ischemic heart disease (IHD) is the number one health threat to women in the USA. While significant advances in female-specific symptoms and pathophysiology have begun to improve mortality rates, a closer look at risk factors across a woman's lifespan needs to be explored. This review targets three time frames: premenopause, pregnancy, and postmenopause. During premenopause, menstrual cycle patterns and estrogen status provide information for IHD risk. Pregnancy conditions provide another window of time that potentially contributes to future cardiovascular risk. Lastly, there is a rise in IHD events and mortality after menopause. Research continues to decipher the impact of estrogen decline at this stage and the effect of menopause hormone therapy as they relate to the cardiovascular health of menopausal women.