During and following acute myocardial infarction, a variety of endogenous mediators are elevated, one of which is adrenomedullin (AM). AM is a multifunctional peptide that has been identified as having a putative beneficial role following an ischemic insult at both systemic and local levels. Classically described as a potent vasodilator, natriuretic, and diuretic agent, experimental infarct models also demonstrate AM to exhibit antiproliferative and antiapoptotic functions in the myocardium, counterregulating the effects of mediators such as angiotensin-II and endothelin-1. Less well documented are the angiogenic and inflammatory modulating potentials of AM, which may also contribute toward reducing adverse ventricular remodeling. The review examines clinical and experimental studies, looking at the effects of AM and cellular mechanisms that could be involved in mediating cardioprotective effects and ultimately optimizing left ventricular remodeling. Finally, the possibility of enhancing endogenous actions of AM by pharmacological intervention is considered.