Leukotrienes are proinflammatory lipid mediators that have been shown to be upregulated in several diseases, including asthma, aspirin-exacerbated respiratory disease (AERD), inflammatory bowel disease, and acute respiratory distress syndrome. Leukotrienes have been explored as therapeutic targets for these diseases and others; however, leukotriene inhibitors have had limited success in the clinic. There are noted differences in the incidence of leukotriene-mediated diseases in males and females, but sex as a factor in the response to leukotriene inhibitors has not been fully explored. In this issue of the JCI, Pace and colleagues present evidence that there are sex-specific differences in the effectiveness of certain leukotriene inhibitors and link the differences in response to the presence of androgens. The results of this study indicate that sex needs to be taken into consideration in the future evaluation of leukotriene inhibitors to treat disease.