Dynamic changes in intracellular Ca2+ levels in vascular smooth muscle cells are critically important for cardiovascular regulation. This Special Topic Issue highlights a series of expert opinion articles focused on this important subject. After a brief overview, novel discoveries surrounding smooth muscle cell Ca2+ influx via L-type and T-type channels are reviewed. Current work revealing the functional importance of dynamic Ca2+ signaling in the control of the parenchymal microvasculature and the emerging role of mitochondrial Ca2+ signaling and store-operated Ca2+ entry in smooth muscle cells is discussed. Finally, recent data describing a new target of localized Ca2+ signaling in arterial myocytes that is responsible for membrane depolarization is reviewed. Authors were encouraged to write in an opinionated and provocative manner with the hope of stimulating discussion in this area of research.