Aromatase (estrogen synthetase) is the enzyme complex responsible for the final step in estrogen synthesis--the conversion of androstenedione and testosterone to estrone and estradiol, respectively. Inhibitors of this enzyme have been shown to be clinically effective in the treatment of advanced breast cancer in postmenopausal women, in whom the major source of estrogen production derives from aromatization of adrenal androgens in peripheral tissues, such as muscle, liver, and fat. The most widely used aromatase inhibitor has been aminoglutethimide; however, it is nonselective and also inhibits adrenocorticosteroid synthesis, necessitating hydrocortisone supplementation. Aminoglutethimide is also associated with frequent and troublesome side effects. Formestane, the first selective aromatase inhibitor to be developed, has an improved safety profile and selectivity, but its use has been limited somewhat by its inconvenient administration via intramuscular injection. In this article, the preclinical and clinical data published to date on the new third-generation aromatase inhibitor anastrozole (Arimidex) are presented in the context of current endocrine therapies. Future applications of aromatase inhibitors, both as monotherapy and in combination with other endocrine therapies, are discussed. The use of aromatase inhibitors in advanced disease, the adjuvant setting, and as possible chemopreventive agents are examined.