Ischemia-reperfusion injury as a general rule is accompanied by dramatic changes in basal and reactive vascular function in most organs. There are similarities in altered organ vascular function, particularly in the first 24 to 48 hours, with decreased basal organ blood flow, hypersensitivity to vasoconstrictor stimuli, attenuated responses to vasodilators, and increased vascular permeability. The reduced responsiveness to endothelium-dependent vasodilators may be due to reduced endothelial NOS activity or to spontaneous maximal activation of NOS/NO activity, which cannot be stimulated further by endothelium-dependent agents. There are also notable quantitative and qualitative differences in ischemia-reperfusion injury vasoreactive response in organs such as kidney, heart, and brain, the basis of which is unexplored, but may reflect regional differences in endothelium and/or organ parenchyma. Further examination of both the mechanisms and consequences of ischemia-reperfusion injury to the vasculature, as well as the clinical implications, should be a rewarding pursuit in organ pathophysiology.