The vesicular transporters for the monoamine and acetylcholine have been successfully targeted for the development of radioligands for human brain imaging. The vesicular monoamine transporter type 2 ligands are based on the structure of tetrabenazine, a known clinically used drug. In contrast, the radioligands for vesicular acetylcholine transporter are based on vesamicol, a toxic xenobiotic. The similarities and differences in the development of these two classes of radioligands are discussed. Copyright © 2013 John Wiley & Sons, Ltd.