Preclinical research indicates that adenosine has important cardiovascular actions including inhibition of vascular inflammation, vascular calcification, atherosclerosis, prevention of ischemia-reperfusion injury and arrhythmias. These actions result from stimulation of specific adenosine receptors located on the cell membrane of various cells including endothelium, vascular smooth muscle cells, cardiomyocytes, autonomic nerve endings and inflammatory cells. Since disease, genetic background and co-medication could modulate the effects, formation and clearance of adenosine, investigations in humans in-vivo is clinically important. However, translation of this preclinical information to humans in-vivo is hampered by autonomic reflexes that occur in particular when adenosine is infused systemically. Furthermore, the rapid uptake of extracellular adenosine by the equilibrative nucleoside transporter into various cell types (including endothelium and erythrocytes) limits the access of intravenously infused adenosine to important target cells such as cardiomyocytes and vascular smooth muscle cells. Therefore, we have operationalized a human in-vivo method to study local actions of adenosine (both exogenous as well as endogenous) in the forearm vascular bed. In this overview, I will provide some examples of this research with particular attention to the effect of adenosine on consequences of ischemia-reperfusion and the effect of statins on the formation of extracellular adenosine. Finally, I will compare some of our forearm results with results from studies in isolated human atrial tissue and with results from clinical trials with clinically relevant cardiovascular endpoints to make the point that knowledge on the clinical pharmacology of adenosine in the forearm is also relevant for the heart.