Pathophysiologic gaps in the actions of currently available treatments for asthma and COPD include neutrophilic inflammation, airway remodeling, and alveolar destruction. All of these processes can be modulated by cyclic adenosine monophosphate-elevating prostaglandins E2 and I2 (also known as prostacyclin). These prostanoids have long been known to elicit bronchodilation and to protect against bronchoconstriction provoked by a variety of stimuli. Much less well known is their capacity to inhibit inflammatory responses involving activation of lymphocytes, eosinophils, and neutrophils, as well as to attenuate epithelial injury and mesenchymal cell activation. This profile of actions identifies prostanoids as attractive candidates for exogenous administration in asthma. By contrast, excessive prostanoid production and signaling might contribute to both the increased susceptibility to infections that drive COPD exacerbations and the inadequate alveolar repair that characterizes emphysema. Inhibition of endogenous prostanoid synthesis or signaling, thus, has therapeutic potential for these types of patients. By virtue of their pleiotropic capacity to modulate numerous pathophysiologic processes relevant to the expression and natural history of airway diseases, prostanoids emerge as attractive targets for therapeutic manipulation.