Aromatase inhibitors and inactivators (AIs) have been/are being widely investigated as an alternative to tamoxifen in the treatment of postmenopausal breast cancer patients. In this paper we have reviewed data from phase III studies to define the role of AIs versus tamoxifen as first-line therapy in patients with metastatic breast cancer, as primary therapy for not operable or early breast cancers not suitable for conservative surgery and as adjuvant treatment for women with early breast cancer. An effort has been performed to evaluate whether specific recommendations were needed for older postmenopausal patients. AIs play a key role in the treatment of advanced breast cancer and represent the agent of choice in patients who are candidates to neoadjuvant hormone-therapy. Longer follow-up of already published trials and additional data coming from ongoing studies will better define when and how to use AIs in the adjuvant setting.