Vascular endothelium is now appreciated to modulate vessel wall structure and function in health and disease. Strategically located between the intravascular space and vessel wall proper, the endothelium has a broad capacity to modify the functional state of adjacent or trafficking cells. Furthermore, recent findings indicate that the endothelium is an interactive tissue capable of responding to numerous mechanical, chemical, and cellular stimuli. The focus of this review will be a discussion of endothelial cell biology in relation to vascular structure and function, with particular emphasis on endothelial modulation of vasomotor tone. It is evident that endothelial cells contribute to the local control of vascular tone by releasing potent vasodilatory mediators, such as endothelium-derived relaxing factor, and vasoconstrictor mediators such as endothelin-1. The endothelium also serves to modify blood-borne signals to which vascular tissues respond. The kidney shares, directly and indirectly, in these events, making this emerging new area a focus of major interest for nephrologists.