Section of Pulmonary and Critical Care Medicine, Department of Medicine, Baylor College of Medicine and the Houston Veterans Administration Medical Center; and Department of Integrative Biology, Pharmacology and Physiology, University of Texas-Houston Health Sciences Center, Houston, Texas ß2-Adrenoceptor agonists (ß-agonists) are the most powerful known bronchodilators, and numerous agents of differing pharmacologic properties are available for clinical use (1–4). Clinicians typically base their choice of a particular agent on the parameters of receptor selectivity and duration of action, but rarely consider intrinsic efficacy. However, a major pharmacologic difference between the long-acting ß-agonists salmeterol and formoterol is the dramatic difference in their intrinsic efficacies. Thus, rational choice between these two agents depends on understanding the clinical significance of this difference. More broadly, possible deleterious effects of the use of ß-agonists on asthma control are often ascribed to the entire class of drugs without consideration of pharmacologic differences among them. In this regard, it is remarkable that both of the New Zealand asthma mortality epidemics were associated with the use of high-dose formulations of ß-agonists of high intrinsic efficacy (first isoproterenol, then fenoterol)(5). However, despite this negative association, an agonist of high intrinsic efficacy might offer advantages in clinical effectiveness over a weak partial agonist. For example, epinephrine and isoproterenol have much higher intrinsic efficacy than albuterol and could be expected to be more clinically effective in severely decompensated asthma in an emergency setting. Because of the potential significance of ß-agonist intrinsic efficacy, both for current treatment of asthma and chronic obstructive pulmonary disease and for ongoing clinical research, we review its pharmacologic determination and clinical implications.