During and after transplantation the kidney experiences a variety of insults that result in functional impairment and structural damage. These changes are mediated or influenced by hormones, cytokines, enzymes and growth factors, which are excreted by endothelial, graft parenchymal as well as by graft infiltrating cells. This review evaluates the pathophysiological role of vasoactive substances (for example, the vasoconstrictors angiotensin II and endothelin, as well as vasodilators such as nitric oxide, adrenomedullin and atrial natriuretic peptide) in kidney transplantation and summarizes recent reports that indicate that targeting vasoactive substances may represent effective therapeutic strategies for the achievement of long-term allograft survival.