The role of adjuvant tamoxifen therapy has gone unchallenged until recently. With the introduction of the selective aromatase inhibitors (AIs), the paradigm for treatment of hormone receptor-positive breast cancer in postmenopausal women is changing. New data from randomized clinical trials have shown the impact of the use of an AI compared with tamoxifen or in sequence with tamoxifen. This review will emphasize some of the highlights from these data sets and the limitations of our current knowledge. Finally, we will discuss the implications of the use of nonselective AIs in the adjuvant setting for the patient who develops recurrent metastatic disease.