The extensive role of adenosine in discriminating input from the extracellular environment is effected through a series of cell membrane-spanning proteins--the adenosine A1, A2A, A2B and A3 receptors. New genetic and epigenetic tools have emerged that facilitate the elucidation of the function of these receptors with greater specificity than is generally possible with traditional antagonist drugs. These tools include antisense oligonucleotides (epigenetic) and gene 'knockin' and 'knockout' mice (genetic) and are discussed in this article by Jonathan Nyce.