Heme oxygenase-derived carbon monoxide (CO) serves as signaling mediator in a wide array of physiological functions to the extent that the beneficial effects elicited by CO gas when administered to mammalian organisms may be exploited for therapeutic purposes (1). In this context, the development of carbon monoxide-releasing molecules (CO-RMs) represents an ideal approach for the delivery of controlled amounts of CO for the treatment of various pathological disorders (2). Transition metal carbonyls and boranocarbonates have been chemically engineered to provide water-soluble compounds that release CO with a fast (CORM-3) or slow (CORM-A1) kinetic (3, 4). The configuration and bioactive features of a range of CO carriers containing manganese, ruthenium , boron and iron are also being investigated in our laboratory to better understand the chemical reactivity of CO-RMs in biological systems. The results collected to date indicate that CO-RMs are pharmacologically active as they possess vasodilatory, hypotensive and anti-inflammatory properties as well as cytoprotective activities. Most recently, we have focused on the idea that CO-RMs could be used clinically to maintain the integrity of organs for transplantation as they have been demonstrated to improve significantly the function of isolated kidneys preserved in cold storage solutions and exert remarkable anti-ischemic effects. Although the mechanism of action of CO-RMs remains to be fully elucidated, we have proposed that a dynamic interaction of CO with specific intracellular metal centers may be the common denominator for the diversified beneficial effects mediated by this gaseous molecule (5). Thus, CO-RMs may help to identify new cellular targets that are responsive to CO and facilitate the therapeutic delivery of this gas in a safe, measurable and controllable fashion.