Much interest has recently been focused on the physiological/pathological role of the heme oxygenase (HO) system, the rate-limiting step in the conversion of heme, in inflammatory events. The HO system may be instrumental in mediating a number of cytoprotective effects, because of its end products, biliverdin, carbon monoxide (CO) and ferrous free iron (Fe2+). As each of the byproducts acts dependently and/or co-operatively with each other, their in vivo effects are complex. In general, the HO system is thought to exert three major functions in ischemia/reperfusion injury: (1) anti-oxidant effects; (2) maintenance of microcirculation; and (3) modulatory effects upon the cell cycle. The anti-oxidant functions depend on heme degradation, oxygen consumption and the production of biliverdin/ferritin via iron accumulation. On the other hand, the production of CO, which has vasodilatory and anti-platelet aggregative properties, can maintain tissue microcirculation. Strikingly, CO may also be instrumental in anti-apoptotic and cell arrest mechanisms. The HO system prevents early injury in the re-perfused organ, and inhibits the function of immune reactive cells, such as neutrophils, macrophages and lymphocytes. The role of the HO system as a novel strategy to mitigate an antigen-independent ischemia/reperfusion injury has been documented in a number of transplantation models.