Over the last decade, elegant studies of the basic biologic characteristics of inflammation and tissue injury have implicated leukocyte-mediated vascular and tissue injury in the pathogenesis of a wide variety of immune and inflammatory clinical disorders, including allograft rejection, adult respiratory distress syndrome, and shock. Recognition of the importance of leukocyte adherence to the endothelium in the pathogenesis of these disorders, in combination with advances in cellular and molecular biology, have led to the development of novel therapeutic approaches to the treatment of immune and inflammatory disorders in which leukocytes contribute to vascular and tissue injury. Several of these promising new therapeutic approaches have focused on the complement system. Examples of this therapeutic approach include the use of monoclonal antibodies directed at leukocyte complement receptors and the administration of soluble complement receptors to inhibit the binding of leukocytes to the endothelium. Because of the biologic and significant potential clinical importance of these advances, in this review, we focus on the complement system and complement receptor-mediated tissue injury.