Adenosine receptors (ARs) are members of the G protein-coupled receptor family and mediate the multiple physiological effects of adenosine. Currently, four AR subtypes have been cloned: A1AR, A2aAR, A2bAR, and A3AR. All subtypes are distinctly distributed throughout the body and AR agonists and antagonists have potential therapeutic utility. Knowledge of AR amino acid structure has been utilized in mutagenesis studies to identify specific receptor regions that interact with distinct classes of ligands. Cloning of ARs has also permitted receptor regulatory processes such as desensitization to be studied in greater detail, in particular, the molecular mechanisms underlying this event. Cloning of the human A1AR has revealed that alternate splicing generates distinct receptor transcripts. The existence of a particular transcript in a tissue or cell apparently regulates the level of A1AR expression in the tissue. This review focuses on these aspects of AR structure and function and their therapeutic regulation.