Inflammation of the airway involves the recruitment of highly active immune cells to combat and clear microbes and toxic factors; however, this inflammatory response can result in unintended damage to lung tissue. Tissue damage resulting from inflammation is often mitigated by resolving factors that limit the scope and duration of the inflammatory response. Both inflammatory and resolving processes require the actions of a vast array of lipid mediators that can be rapidly synthesized through a variety of airway resident and infiltrating immune cells. Eicosanoids and endocannabinoids represent two major classes of lipid mediators that share synthetic enzymes and have diverse and overlapping functions. This review seeks to provide a summary of the major bioactive eicosanoids and endocannabinoids, challenges facing researchers that study them, and their roles in modulating inflammation and resolution. With a special emphasis on cystic fibrosis, a variety of therapeutics are discussed that have been explored for their potential anti‐inflammatory or proresolving impact toward alleviating excessive airway inflammation and improving lung function.