I/R is an important non-immunological, antigen independent factor influencing graft outcome. In addition to its non-specific effects it potentiates graft immunogenicity and increases host alloresponsiveness. Originally considered an event surrounding organ procurement, preservation and revascularization, it has recently been associated with donor conditions such as brain death and the non-heart-beating donor. Occurring early in the transplant process, it initiates a cascade of molecular and cellular events including the release of proinflammatory mediators and attraction of various cell types infiltrating the tissues. As a consequence, acute and chronic changes develop which influence structure and function of the organ which may contribute to reduced graft survival. Eventually, attentuation of I/R by strategies interfering with the different processes promoted by this insult may constitute a means to improve both short and long-term graft outcome.