Many patients with chronic obstructive pulmonary disease (COPD) continue to experience exacerbations despite receiving standard-of-care treatments. Novel approaches to COPD treatment focus on understanding and targeting molecular mechanisms of airway inflammation, airway obstruction, remodeling and lung destruction. Several identified phenotypes and endotypes of COPD will pave the future path for a more personalized approach to therapy. Although well known to be associated with neutrophilic inflammation, COPD may also be driven by eosinophilic inflammation both at stable states and during exacerbation. Targeting eosinophilic inflammation has been successful in managing severe eosinophilic asthma and may hold promise in certain phenotypes of COPD. The most promising biologic treatments at an advanced stage of development are agents blocking interleukin (IL)-5 or its receptor. This review examines our current understanding of the eosinophilic inflammation in COPD and the rationale for IL-5 targeting agents.