The latest generation of nonsteroidal aromatase inhibitors (anastrozole and letrozole) has been approved by the US Food and Drug Administration for use in the first- and second-line treatment of postmenopausal women with hormone receptor-positive (or unknown) breast cancer. The steroidal agent exemestane is approved for second-line treatment and is currently being evaluated for first line. In addition, these agents are being evaluated in the adjuvant and neoadjuvant settings. Because preclinical studies have suggested some differences in the efficacy of these agents to inhibit aromatase, it has been important to evaluate whether these properties actually translate into meaningful differences in the clinical setting. The pharmacokinetic properties of each aromatase inhibitor influences their ability to perform effectively. Examination of the data suggests differences in uptake rates, half-life of elimination, metabolism, and clearance rates that could influence their efficacy. However, the significance of these differences for clinical effectiveness over long-term use remains to be determined.