New therapeutic monoclonal antibodies targeting the IL-5/IL-5 receptor pathway are extremely efficient in depleting blood eosinophils from subjects with asthma. In asthma, these anti-IL-5 therapies reduce exacerbations by 50% in eosinophilic severe asthma, but they are not available for patients with milder eosinophilic asthma. In addition, it is well known that these therapies do not totally deplete lung eosinophils and do not seem to change their phenotype [1,2]. Eosinophils are produced in IL-5 knock-out mice, and patients receiving neutralizing anti-IL-5 therapies retain a stable population of residual blood eosinophils closely similar to those of healthy individuals [3,4]. In fact, it is uncertain whether the lack of complete depletion of either residual or activated eosinophils is beneficial or detrimental for patients. Despite the advantage of the anti-IL-5 specificity on eosinophils, the redundancy of the three beta chain receptor cytokines (IL-3, IL-5 and GM-CSF) on eosinophils is well known and may explain the lack of complete depletion of eosinophils [5]. However, in mouse, blockade of the common beta chain receptor did not completely deplete the presence of terminally differentiated eosinophils in the blood [6], suggesting that other factors can differentiate and mature eosinophils. Of note, asthma is only one of numerous eosinophilic diseases, and anti-IL-5 therapies have not yet proven their clinical efficacy to treat most of these devastating diseases. In this Special Issue, several original studies and reviews point out the necessity to continue our efforts to better characterize the heterogeneity of precursor and mature eosinophil populations and to provide new insights regarding other therapeutic targets, which would act on the differentiation and activation of general and specific eosinophil populations.....