In 2005, cancer accounted for 13% of all deaths worldwide. Breast cancer is the number-one cause of cancer-related death among women in the USA, affecting 178,480 of them in 2007. As 75% of tumors in postmenopausal women and half in premenopausal women express estrogen receptor, endocrine therapy plays a significant role as a systemic treatment. Robust datasets have demonstrated the impact of tamoxifen in reducing breast cancer recurrence and mortality, regardless of the age of the patient. Other estrogen-deprivation strategies, such as aromatase inhibitors in postmenopausal women and luteinizing hormone-releasing hormone agonists in premenopausal women, are being increasingly used for estrogen receptor-positive breast cancer. This review discusses basic principles regarding endocrine therapy, the need for accurate estrogen receptor testing and the role of menopause in therapy selection.