This review summarizes the status of 2 major clinical trials involving exemestane, a nonsteroidal inactivator of aromatase. The first trial, Intergroup Exemestane Study (IES), has been previously reported. More than 4700 postmenopausal women were randomized to receive exemestane versus continued tamoxifen at 2-3 years into 5 years of adjuvant tamoxifen. In the hormone receptor-positive group, there was a one-third improvement in disease-free survival and a near survival advantage (P = 0.08) for the crossover strategy. The second trial is the Tamoxifen Exemestane Adjuvant Multicenter (TEAM) study. Recently, the design was modified to take into account the information from the IES. In the initial phase of TEAM, 7000 patients were randomized to receive 5 years of exemestane versus 5 years of tamoxifen. With the IES results, TEAM was modified so that 5 years of exemestane would be compared with 5 years of tamoxifen crossed over to exemestane. An additional 2500 patients have now been accrued. Updates of the IES and the first report of the TEAM might be available in 2006. The implications of these studies are discussed in this article.