The role of eosinophils in allergic inflammation is well recognized. In homeostasis these cells are found in multiple healthy tissues including the lung parenchyma, but the function of these resident eosinophils is unknown. Circulating eosinophils are easily quantifiable and have been used to define “eosinophilic phenotype”, and to select patients who are likely to respond to anti-eosinophil and anti-Th2—directed therapies. However, presence of eosinophils in circulation may not necessarily indicate that the eosinophils are key effector cells for an airway disease such as asthma and this may be reason for not all patients responding well to anti-IL5 therapies despite normalization of blood eosinophils. This pro-con commentary examines the role of enumerating circulating vs luminal (sputum) eosinophils (and their activation status) not only to initiate therapies with monoclonal antibodies, but to monitor their clinical response while on therapy.