Heart disease is the number one killer of men and women in the world. The incidence of cardiovascular disease is known to be much higher in men than women until around the ages of 60-75 years, when the occurrence of the disease becomes approximately equal in both sexes. Additionally, the occurrence of heart disease is significantly lower in premenopausal women than postmenopausal women. Since men have a higher risk for heart disease than women until 10-15 years after the average age of menopause and postmenopausal women have a higher risk of cardiovascular disease than premenopausal women, it is hypothesized that endogenous estrogen exposure throughout the fertile period of a woman's life postpones the onset of cardiovascular disease. Research shows estrogen has beneficial effects on the cardiovascular system by regulating multiple metabolic processes including lipid metabolism, vasodilation, nitric oxide synthesis, cytochrome c apoptosis, and mitochondrial antioxidant production. Though estrogen has been found to have cardiovascular benefits on individual metabolic processes, the treatment of synthetic estrogen on postmenopausal women and men to reduce the overall risk of heart disease is very controversial. The controversy of synthetic estrogen is partially due to the fact that most studies done using estrogen replacement therapy on postmenopausal women and men resulted in either no effects or harmful effects on the cardiovascular system. Hormone replacement therapy has also been associated with a higher risk of multiple medical conditions, especially venous thromboembolism and breast cancer. This review will explore these topics and consider the costs and benefits of estrogen replacement therapy.