Aromatase inhibitors (AIs) are a class of compounds that inhibit the cytochrome P450 aromatase enzyme that mediates conversion of androgens to estrogen in the adrenal gland. AIs have been approved for second-line and, more recently, first-line treatment of advanced breast cancer in postmenopausal women. The most recent, third generation of AIs are the non-steroidal agents anastrozole (Arimidex) and letrozole, and the steroidal compound exemestane. As second-line therapy, anastrozole demonstrated a significant survival advantage over megestrol acetate (26.7 months v.s. 22.5 months; p < 0.025).="" exemestane="" also="" produced="" better="" survival="" than="" megestrol="" acetate,="" although="" these="" data="" were="" less="" mature.="" letrozole="" 2.5="" mg="" has="" not="" demonstrated="" a="" survival="" advantage="" versus="" megestrol="" acetate="" in="" the="" second-line="" setting.="" as="" first-line="" therapy,="" anastrozole="" has="" demonstrated="" significant="" superiority="" in="" response="" rates="" with="" respect="" to="" time="" to="" progression="" (ttp)="" (11.1="" months="" v.s.="" 5.6="" months;="">p = 0.005) and has also demonstrated significantly greater clinical benefit rates compared with tamoxifen (59.1% v.s. 45.6%; p = 0.0098). Letrozole has also demonstrated significantly longer TTP than tamoxifen in the first-line setting (9.5 months v.s. 6 months; p = 0.0001). Important differences between the pharmacological profiles of these agents have been noted, particularly with respect to their effects on glucocorticoid metabolism; data for individual agents should not be extrapolated from one to another, particularly in the adjuvant setting.