Cardiovascular disease is a leading cause of death and disability and despite advances in treatment there remains an ongoing need to develop new therapeutic interventions. Accumulating evidence points towards an important role for the adrenomedullin (AM) family of peptides in pressure/volume homeostasis and indicate potential as therapeutic agents in a variety of clinical settings including cardiovascular disease. Plasma levels of AM are raised in cardiovascular disease in proportion to severity of cardiac dysfunction and are useful prognostic indicators of outcome. AM administration in both experimental and human heart failure induces a beneficial spectrum of biological action including reduced arterial and atrial pressures, improved cardiac output, inhibition of plasma aldosterone and preservation or augmentation of urinary sodium excretion. Experimental data also supports a role for AM in cardioprotection in cardiac ischemia/reperfusion injury and in the progression of heart failure following myocardial infarction. Thus, strategies to manipulate the AM system may prove beneficial as adjunctive therapy in cardiovascular disease.