Third-generation aromatase inhibitors and inactivators have been successfully implemented in therapy of metastatic breast cancer, and three large phase III trials have revealed superiority compared with tamoxifen monotherapy in the adjuvant setting. Notably, each of these trials recorded a substantial reduction in contralateral breast cancer among patients exposed to the aromatase inhibitor/inactivator. A major concern in implementing use of these compounds in the preventive setting relates to potential detrimental effects of estrogen suppression on bone and lipid metabolism. Recent data from a placebo-controlled study now reveal 2 years of treatment with exemestane compared with placebo to have moderate effects on bone metabolism and plasma lipid profile, supporting further evaluation of exemestane as a potential preventive agent for breast cancer in postmenopausal women.