Aminoacyl-tRNA synthetases are key enzymes in protein biosynthesis that catalyze aminoacylation of their cognate tRNA. During their long evolution, these ancient enzymes incorporated new domains by insertioos or fusions to the class-defining catalytic core to attend more functions. Recently, fragments of the closely related human tyrosyl- and tryptophanyl-tRNA synthetases were discovered to be active in angiogenesis signaling pathway. One synthetase fragment has proangiogenic activity, while the other is antiangiogenic. These two tRNA synthetases link protein synthesis to a major cell-signaling pathway in the given mammalian cells. The results with animals suggest that therapeutic applications for many human diseases such as neovascular eye disease and tumor are possible with these tRNA synthetases.