In their study published in this issue of Academic Medicine, Costa and colleagues confirmed the underlying constructs of the Interpersonal Reactivity Index (IRI) and the Jefferson Scale of Empathy (JSE) in medical students. The authors of this Commentary propose that in comparing two instruments that both purport to measure empathy, researchers or test users must pay close attention to the target populations, the conceptualizations of empathy, and the validity evidence in relation to pertinent criterion measures. The Commentary’s authors draw attention to the fact that the IRI was developed for administration to the general population, whereas the JSE was developed specifically for administration to students and practitioners of health professions. Also, the author of the IRI conceptualized empathy as a combination of cognitive and emotional attributes, whereas the authors of the JSE defined empathy as a predominantly cognitive attribute. These differences are reflected in the content of the items, which determines the underlying constructs of the two instruments. The Commentary authors suggest that any empathy-measuring instrument in the context of health professions education and patient care requires the crucial evidence of significant relationships with indicators of clinical competence and positive patient outcomes. Such validity evidence is readily available for the JSE, and the Commentary authors recommend that researchers make efforts to provide pertinent validity support for any other instrument measuring empathy in health professionals-in-training and in-practice.