Letrozole (Femara™) is a highly selective oral non-steroidal aromatase inhibitor. According to in vitro data, letrozole is 170-fold more potent in inhibiting aromatase than aminoglutethimide (AG) and 19-fold more active than anastrozole. Letrozole effectively inhibits intratumoral aromatase according to in vitro and in vivo data. It is indicated for the treatment of advanced breast carcinoma in post-menopausal women who have failed prior anti-estrogen therapy. Final FDA approval was granted in 1997. In two randomized phase IIb/III studies in patients previously treated with an antiestrogen, 19.5% and 23.6% of patients achieved an objective response with letrozole 2.5 mg/day compared with 12.4% receiving AG and 16.4% of patients receiving megace. Median overall survival was increased in the letrozole 2.5 mg/day group by 8 months compared to AG and by 3 months compared to megace. The lower 0.5 mg/day dose of letrozole was associated with poorer response rates and overall survival in both studies.