Adenosine is an endogenous purine nucleoside that is an important metabolic sensing molecule. It is released during conditions of low oxygen delivery to tissues and organs to activate a range of effects in vascular tissues. Adenosine has a role in the vasculature by mediating vasodilation, vessel remodelling, cell proliferation as well as antiplatelet and inflammatory responses. Also, adenosine stimulates vasculogenesis and angiogenesis during wound healing and tumour growth. Currently, the clinical uses of adenosine are limited to treatment of supraventricular tachycardia or as a coronary vasodilator during radionuclide myocardial perfusion imaging. Due to the involvement of adenosine in various pathological conditions, the targeting of specific adenosine receptor (ADOR) subtypes in the vasculature using selective ADOR agonists or antagonists could have potential therapeutic benefit. However, the distribution of the receptors differs between species. Therefore, cross-species testing is essential to validate drug function.