Tamoxifen has long been the standard endocrine therapy for postmenopausal women with hormone-sensitive breast cancer. However, data now suggest that the third-generation aromatase inhibitors have emerged as superior alternatives for advanced disease. In early disease evaluation of initial adjuvant therapy, data from the Arimidex((R)), Tamoxifen, Alone and in Combination trial has shown that anastrozole is more effective than tamoxifen with a better risk-benefit profile. This trial provides the most mature data of any aromatase inhibitor study and suggests that anastrozole should be considered the preferred initial adjuvant therapy for postmenopausal women with hormone-responsive early breast cancer. The emergence of aromatase inhibitors as an alternative to tamoxifen for the treatment of breast cancer is challenging the management of the disease and influencing the change of regulatory guidelines.