Breast cancer is the most common malignant neoplasm affecting women in Western countries, and most new cases are manifested during the postmenopausal period. The clinical results obtained with aminoglutethimide, and later with formestane, have established aromatase inhibition as one of the major therapeutic options in hormone-dependent advanced disease. Nevertheless, the lack of specificity of aminoglutethimide and the less than optimal oral activity of formestane soon led to further efforts to find a potent, highly selective, orally active, side-effect-free aromatase inhibitor for use in postmenopausal women with advanced breast cancer. Here we review the available data on three new, competitive non-steroidal aromatase inhibitors –- letrozole, vorozole and anastrozole –- which are approaching the point of detailed pharmacologic and clinical evaluation. Preliminary data have confirmed the high potency and selectivity of these endocrine agents, but their antitumor activity still remains to be completely defined. Challenges given by these novel aromatase inhibitors are discussed taking into account the biologic implications related to their mechanism of action and their future use in the management of breast cancer.