The current issue of CHEST (see page 20) contains a thought-provoking article by Gabler and colleagues1 entitled, “Race and Sex Differences in Response to Endothelin Receptor Antagonists for Pulmonary Arterial Hypertension.” Gabler and colleagues1 make an important observation regarding sex differences that has widespread implications in the treatment of pulmonary arterial hypertension (PAH). They report a pooled analysis of patient-level data from six randomized placebo-controlled trials of endothelin receptor antagonists (ERAs) that looked for heterogeneity in the treatment response. All of these drugs are approved as treatments for PAH, without any specific recommendations related to their efficacy in subgroups of patients. Yet, the findings suggest that sex, and possibly race, may influence the response to ERA treatment of PAH. Specifically, women not only had a significantly greater response in terms of change in 6-min walk distance (6MWD) than did men, but women also experienced deteriorations in 6MWD when assigned to placebo, whereas men did not. This raises several important questions related to PAH and its treatment. Is the underlying pathobiology of PAH different in men vs women? Are these drugs metabolized differently in men vs women, which would account for the findings? Are the efficacies of other drugs for PAH also different in men vs women?