At least 25 years ago, ATP had been widely recognized as co-transmitter to noradrenaline in sympathetically innervated tissues, in general, and in blood vessels, in particular. Meanwhile, seven subunits of ionotropic P2X receptors and eight different G protein-coupled P2Y receptors have been identified. Several of these P2 receptors have been reported to mediate vasocontraction and/or vasorelaxation. In the smooth muscle cells, ionotropic P2X₁ receptors mediate fast and transient neurogenic vasoconstriction. Activation of mainly P2Y₁₂, but also of P2Y_1,2,4,6, mediates long lasting vasoconstriction. In addition, activation of endothelial P2Y receptors (mainly P2Y₁) has been shown to mediate vasodilatation via NO, prostacyclin, and endothelium-derived hyperpolarizing factor. Concerning the classical sympathetic transmitter noradrenaline, it is well known that presynaptic inhibitory a₂ and facilitatory b₂ receptors are responsible for the fine-tuning of the neuro-vascular transmission. For nucleotides, evidence has been obtained that presynaptic P2Y₁₂ receptors mediate an inhibition, while presynaptic P2X₂ and P2Y₁ receptors mediate a facilitation of sympathetic transmitter release. Further complexity is added to the regulatory system of nucleotide receptors at the neuro-vascular interface by direct interactions between different P2Y receptors and between P2Y receptors and ectonucleotidases. Together, the data summarized here show that the co-transmitter ATP is much more versatile than the original neuro-vascular transmitter noradrenaline.