Despite maximal medical therapy, a subset of patients with chronic obstructive pulmonary disease continue to suffer acute exacerbations. It is also clear that a subset of this population has elevated blood eosinophils. In addition to clearly responding better to inhaled corticosteroids, it is also possible that this subgroup may benefit from biologic treatments targeting eosinophilic inflammation. Mepolizumab, a humanized monoclonal antibody against interleukin-5 (IL-5), may have a therapeutic effect in a subgroup of patients with COPD and eosinophilic airway inflammation. In this review, we discuss the biologic rationale for mepolizumab targeting IL-5 in eosinophilic COPD as well as the results of recently published clinical trials.