AbstractPlatelet‐activating factor (PAF) is a phospholipid‐derived mediator with an established role in multiple inflammatory states. PAF is synthesized and secreted by multiple cell types and is then rapidly hydrolyzed and degraded to an inactive metabolite, lyso‐PAF, by the enzyme PAF acetylhydrolase. In addition to its role in platelet aggregation and activation, PAF contributes to allergic and nonallergic inflammatory diseases such as anaphylaxis, sepsis, cardiovascular disease, neurological disease, and malignancy as demonstrated in multiple animal models and, increasingly, in human disease states. Recent research has demonstrated the importance of the PAF pathway in multiple conditions including the prediction of severe pediatric anaphylaxis, effects on blood–brain barrier permeability, effects on reproduction, ocular diseases, and further understanding of its role in cardiovascular risk. Investigation of PAF as both a biomarker and a therapeutic target continues because of the need for directed management of inflammation. Collectively, studies have shown that therapies focused on the PAF pathway have the potential to provide targeted and effective treatments for multiple inflammatory conditions.