Platelet-activating factor (PAF) is a pro-inflammatory lipid mediator possessing a unique 1-O-alkyl glycerophospholipid (GPC) backbone (I-O-alkyl-2-acetyl-sn-glycero-3-phosphocholin). Cloned PAF receptor, which belongs to the G protein-coupled receptor superfamily, transduces pleiotropic functions including cell motility, smooth muscle contraction, and synthesis and release of mediators and cytokines via multiple heterotrimeric G proteins. Pharmacological studies have suggested that PAF functions in a variety of settings including allergy, inflammation, neural functions, reproduction, and atherosclerosis. Establishment of PAFR mice confirmed that the PAF receptor is responsible for pro-inflammatory responses, but that its roles in other settings remain to be clarified.