Research findings are unveiling the potential role of leukocytes and leukocyte adhesion molecules such as selectins in ischemia-reperfusion injury (IRI). "Anti-adhesion" therapy using selectin blocking agents may represent a new approach to treatment of the many diverse clinical disorders in which ischemia-reperfusion occurs, including transplantation, reperfusion after thrombotic events and shock. In this paper we review the pathophysiology of IRI, the different types of selectins and selectin ligands, the clinical implications of selectin blockade in different organs with IRI, and new insights into mechanism of action.