Endothelium-dependent changes in vasomotor tone, whether evoked by vasoactive agents or physical forces, are recognized as essential for the local hemodynamic control in various normal and pathological circumstances. They are based on a complex signaling network within the vascular wall. In recent years, substantial efforts have been made to analyze how such signals are generated and used in the endothelium-dependent control of vascular smooth muscle. The underlying mechanisms vary with species, age, sex, hormonal status, vascular bed studied, caliber of the blood vessels, triggering stimuli, pre-existing vascular tone, oxidative stress, and pathology. Such aspects and many others will be addressed specifically by the authors contributing to this volume.