Patients with heart failure have frequently been reported to show elevated levels of plasma adrenomedullin. These levels generally correlate with severity of hemodynamic dysfunction and also with neurohormonal indices which are activated according to the severity of heart failure. Furthermore, adrenomedullin gene expression in the heart and kidney is increased in experimental and clinical heart failure. A small number of studies have examined the responses to infusion of adrenomedullin in experimental and clinical heart failure. These studies have generally shown that infusion of adrenomedullin has beneficial hemodynamic effects and promotes maintenance or improvement in renal function, although most of these trials were of short duration. The available data suggest that adrenomedullin in the heart, kidney and plasma is increased in heart failure, possibly to counter the activation or actions of vasoconstricting and sodium-retaining hormone systems. An improved understanding of the role of adrenomedullin in heart failure might lead to the development of therapeutic agents acting through adrenomedullin receptors.