Many neurohumoral factors play important roles in the regulation of the cardiovascular system and in the pathophysiology of cardiovascular disease. Adrenomedullin (AM) is a potent vasodilatory peptide originally discovered in the acid extract of human pheochromocytoma tissue but now known to exert a variety of effects within the cardiovascular system. AM expression is widely distributed throughout the cardiovascular system and has been identified in the heart, lungs, blood vessels and kidneys. In addition, the co-localization of AM and its receptor components suggest AM acts as an autocrine and/or paracrine factor to play a key role in the regulation of cardiovascular function. Evidence also strongly suggests that cardiovascular disease is associated with elevated levels of AM in plasma and tissue. In this review, we describe the pathophysiological changes in plasma and local AM associated with myocardial infarction, heart failure and pulmonary hypertension. We also describe the clinical application of AM in cardiovascular disease from the viewpoints of diagnosis and treatment.