The resolution of inflammation in healthy airways is an active process, with specialized mediators and cellular mechanisms enlisted to restore tissue homeostasis. This article focuses on recent discoveries of natural mediators derived from essential fatty acids, including ω-3 fatty acids, with anti-inflammatory and pro-resolving. These pro-resolving mediators serve as agonists at specific receptors. Asthma is an incurable disease of chronic, nonresolving inflammation of the airways. While the biosynthesis of pro-resolving mediators occurs during asthma, defects in their production are associated with disease severity, suggesting that the pathobiology of asthma may result in part from impaired resolution of airway inflammation.