A recent National Institutes of Health consensus guideline recommends the general use of adjuvant hormonal therapy for the treatment of early breast cancer in postmenopausal women with estrogen receptor-positive tumors. Standard therapy has been 5 years of tamoxifen, but about 30% of those patients fail to survive 10 years, many as a consequence of tamoxifen resistance. Promising results with the third-generation aromatase inhibitors anastrozole, letrozole, and exemestane in first- and second-line treatment of metastatic breast cancer has prompted their evaluation as adjuvant therapy in patients progressing on tamoxifen or as alternative first-line treatment. Anastrozole has recently achieved significantly longer disease-free survival than tamoxifen in a first-line adjuvant therapy trial, and letrozole is being investigated in several large adjuvant trials. Aromatase inhibitors appear to be well tolerated for long-term adjuvant treatment. In the neoadjuvant setting, letrozole has been especially effective compared with tamoxifen in downstaging primary tumors in postmenopausal women, permitting significantly more breast-conserving surgery.