Compelling evidence has demonstrated that the eosinophils bring negative biological outcomes in several diseases, including eosinophilic asthma and hypereosinophilic syndromes. Eosinophils produce and store a broad range of toxic proteins and other mediators that enhance the inflammatory response and lead to tissue damage. For instance, in asthma, a close relationship has been demonstrated between increased lung eosinophilia, asthma exacerbation, and loss of lung function. The use of an anti-IL-5 therapy in severe eosinophilic asthmatic patients is efficient to reduce exacerbations. However, anti-IL-5-treated patients still display a relatively high amount of functional lung tissue eosinophils, indicating that supplemental therapies are required to damper the eosinophil functions. Our recent published works suggest that compared to IL-5, IL-3 can more strongly and differentially affect eosinophil functions. In this review, we summarize our and other investigations that have compared the effects of the three β-chain receptor cytokines (IL-5, GM-CSF and IL-3) on eosinophil biology. We focus on how IL-3 differentially activates eosinophils compared to IL-5 or GM-CSF.