Adrenomedullin (AM) is a multi-functional peptide discovered in human pheochromocytoma. Initially, it was suggested that AM was synthesized only by tumor cells, however, subsequent studies revealed that it was produced also by normal adrenal medulla as well as by many other tissues. Now it is well established that AM functions as a circulating hormone and local paracrine mediator with multiple biological activities. AM stimulated cAMP production in human platelets and exerted potent and long-lasting hypotensive activity in the rat. AM is a physiologically relevant regulator in fluid and electrolyte homeostasis; inhibition both water and salt intake, increase renal blood flow, and cause diuresis and natriuresis. The up-regulation of cardiac AM system in hypertension may be a protective mechanism decreasing myocardial overload due to vasodilatory and natriuretic properties of AM, as well as limiting further myocardial hypertrophy and remodeling. AM may protect the kidney against ischemia-reperfusion injury. AM is also suggested as antiapoptotic, anti-inflammatory and angiogenic factor. In this review, I offer a review of our current knowledge on AM and give the putative role of AM in water-electrolyte balance, hypertension and kidney disease.