Aminoacyl-tRNA synthetases are modular proteins, with domains that have distinct roles in the aminoacylation reaction. The catalytic core is responsible for aminoacyl adenylate formation and transfer of the amino acid to the 3' end of the bound transfer RNA (tRNA). Appended and inserted domains contact portions of the tRNA outside the acceptor site and contribute to the efficiency and specificity of aminoacylation. Some aminoacyl-tRNA synthetases also have distinct editing activities that are localized to unique domains. Efficient aminoacylation and editing require communication between RNA-binding and catalytic domains, and can be considered as a signal transduction system. Here, evidence for domain-domain communication in aminoacyl-tRNA synthetases is summarized, together with insights from structural analysis.