Various imidazoline and guanidinium derivatives elicit diverse cellular responses in peripheral and nervous tissues that are often difficult to attribute to known receptor signalling systems. Biochemical, functional and clinical evidence suggests that some activities of these compounds may be related to their action on defined imidazoline binding sites, which have been recently characterized. Unexpectedly, and of particular significance, recent data indicate that two members of the family of imidazoline binding sites are identical to the A and B isoforms of monoamine oxidase. In this article, Angelo Parini and colleagues summarize the evidence for the characterization and location of imidazoline binding sites, and speculate on the clinical implications of compounds acting on these sites.