Adrenomedullin (AM), a vasodilatory peptide, has recently been shown to have multipotent properties. Among its other pharmacological actions, AM has been hypothesized to protect organs from hypertension, hypoxia, or infection. In vitro studies have shown that AM has an inhibitory effect on vascular smooth muscle cell proliferation and oxidative stress, but that it enhances nitric oxide (NO) production, which in turn is thought to protect against organ damage. Recent advances in genetic engineering have made it possible to investigate the chronic effects of AM in vivo. Applying genetic engineering, it is revealed that adrenomedullin was shown to protect liver, kidney, vasculature, and heart from septic shock, ischemia and hypertension. However, speculation as to the mechanism of its organ-protective effect varies from report to report. Possible mechanisms include preservation of blood flow, interaction with NO and/or oxidative stress. And although there continue to be technical limitations to the use of these genetically modified models, their application in further investigations should help to clarify the potential efficacy of AM as a new therapeutic agent.