Several compounds that selectively inhibit estrogen synthesis via aromatase have been developed. Steroidal substrate analogs, such as formestane and exemestane, inactivate aromatase by binding irreversibly to it. Non-steroidal inhibitors, such as the triazole compounds letrozole and anastrozole, are highly potent, reversible inhibitors with good specificity for aromatase. The intratumoral aromatase model for postmenopausal breast cancer has been used to investigate the efficacy of letrozole, anastrozole and exemestane in combination and sequentially. Combining letrozole or arimidex with tamoxifen or faslodex was not more effective than the aromatase inhibitors alone, but was more effective than tamoxifen alone. Letrozole was superior to and longer lasting than the other agents, suggesting that aromatase inhibitors control tumor growth effectively by inducing greater tumor response and extending treatment time. In addition, aromatase inhibitors can be effective in patients relapsing from tamoxifen. Because two types of aromatase inhibitors are available, steroidal enzyme inactivators and reversible non-steroidal inhibitors in sequential therapy could be useful if resistance to one type develops.