During the past years a number of potent and selective antagonists for the human A(3) adenosine receptor (AR) have been developed, including tricyclic compounds, such as triazoloquinazoline, pyrazolo-triazolopyridine, imidazopurinone, triazoloquinoxaline and pyrazoloquinoline derivatives. Bicyclic compounds include isoquinoline and related quinazoline derivatives. Monocyclic dihydropyridine and pyridine also proved to be potent selective A(3) AR antagonists. So far, no potent, selective antagonist is available for rodent A(3) ARs. Most of the A(3) AR antagonists are highly lipophilic and exhibit very poor water-solubility. Potential therapeutic applications for A(3) AR antagonists include inflammatory diseases, asthma, stroke, and glaucoma.