Initially identified in the parathyroidea, the calcium sensing receptor (CaSR) is now recognized as an ubiquitously expressed receptor that exerts specific functions in multiple organs including the cardiovascular system. This review will focus on the role that CaSR plays in vascular and cardiac tissues. In the vasculature, CaSR is expressed in endothelial and smooth muscle cells. CaSR of endothelial cells participates in part to the regulation of local perfusion by linkage of CaSR activation to endothelial hyperpolarization and nitric oxide release. CaSR of smooth muscle cells is involved in the control of proliferation. In the pulmonary vasculature, however, CaSR participates in the onset of pulmonary hypertension, making CaSR antagonism a therapeutic option in this case. In the heart, CaSR is expressed in cardiac fibroblasts and myoyctes, contributing to normal cardiac function and composition of extracellular matrix. More important, activation of CaSR may participate in the cardiac protective effects of ischaemic pre-conditioning. In conclusion, CaSR plays an important physiological role in many regulatory pathways of the cardiovascular system, but due to the complex interaction between various cardiovascular cells and cell-specific effects, use of activators or inhibitors of CaSR for treatment of specific disease forms is yet not on the way.