▪ Abstract The functional impact of ion channels in vascular endothelial cells (ECs) is still a matter of controversy. This review describes different types of ion channels in ECs and their role in electrogenesis, Ca2+ signaling, vessel permeability, cell-cell communication, mechano-sensor functions, and pH and volume regulation. One major function of ion channels in ECs is the control of Ca2+ influx either by a direct modulation of the Ca2+ influx pathway or by indirect modulation of K+ and Cl− channels, thereby clamping the membrane at a sufficiently negative potential to provide the necessary driving force for a sustained Ca2+ influx. We discuss various mechanisms of Ca2+ influx stimulation: those that activate nonselective, Ca2+-permeable cation channels or those that activate Ca2+-selective channels, exclusively or partially operated by the filling state of intracellular Ca2+ stores. We also describe the role of various Ca2+- and shear stress-activated K+ channels and different types of Cl− channels for the regulation of the membrane potential.