Although the aromatase inhibitors (AIs) as a class exhibit clear differences in terms of their structure and mechanism of action, these differences do not always translate into clinically significant differences in patient outcomes. In fact, these differences may actually reflect differences in clinical trial design (i.e. upfront, sequential or switch therapy) or the patient population studied. The results of clinical trials demonstrate a clear superiority of third-generation AIs over tamoxifen. It will, however, be necessary to wait for the results of the ongoing head-to-head MA.27 and Novartis trials to determine whether there is any differentiation between the various third-generation AIs.