Adrenomedullin is a highly conserved vasoactive peptide participating in a variety of physiological and pathophysiological processes including pregnancy, embryonic development, tumor progression and regulation of vascular tone. In particular, adrenomedullin expression is widely distributed throughout the cardiovascular system including heart, lungs, blood vessels and kidneys. The observation that adrenomedullin co-localizes with its receptors suggests that the peptide may act as an autocrine and/or paracrine factor in the regulation of cardiovascular function. In this review, we described the pathophysiological changes in plasma and local adrenomedullin associated with vascular endothelial function and the signaling mechanisms involved. Recent evidence has depicted a unique role of adrenomedullin in the regulation of vascular endothelial function in part through regulation of cAMP, cGMP and intracellular Ca2+ mobilization. This review summarized vascular endothelial actions of adrenomedullin under both physiological and pathophysiological conditions in an effort to provide guidance for the clinical application of adrenomedullin in vascular diseases.