Over the last decade, many reports have discussed aminoacyl-tRNA synthetases (ARSs) in extracellular space. Now that so many of them are known to be secreted with distinct activities in the broad range of target cells including endothelial, various immune cells, and fibroblasts, they need to be classified as a new family of extracellular signal mediators. In this chapter the identity of the secreted ARSs, receptors, and their physiological and pathological implications will be described.