Aminoacyl-tRNA synthetases (codases) catalyze aminoacylation of a particular tRNA with the corresponding amino acid at the first step of protein biosynthesis. The review considers the universal structural and functional characteristics of this largest family of enzymes, partitioned into two classes. The modes of tRNA binding and recognition, as well as additional editing activity, which are responsible for the extremely high fidelity of aminoacyl-tRNA synthesis, are discussed. The available data suggest an unusual evolutionary history for the most important components of the mechanism that ensures the proper synthesis of proteins and the association of this mechanism with amino acid biosynthesis. In addition, the review considers the secondary functions of synthetases in various cell metabolic processes, including pathophysiological ones. Their investigation may help to develop new diagnostic techniques and therapies.