The major dysfunction of capillaries after prolonged periods of ischemia is the lack of re-establishment of nutritive blood flow upon onset of reperfusion, i.e., capillary no-reflow. Several mechanisms have been proposed to cause capillary no-reflow, including intravascular hemoconcentration and thrombosis, leukocyte plugging, endothelial cell swelling, vasomotor dysfunction, and interstitial edema formation. Electron microscopic studies suggest that thrombus formation and intravascular clotting are not significant mechanisms. Moreover, intravital microscopic studies have demonstrated that plugging of capillaries by leukocytes is not a primary cause for the manifestation of no-reflow in postischemic striated muscle. In contrast, both in vivo studies and histological examinations support the concept that ischemia/reperfusion induces the disruption of the endothelial integrity with loss of fluid to endothelial cells and the interstitial space. As a consequence, these pathological sequelae are associated with intravascular hemoconcentration, endothelial cell swelling and interstitial edema formation, which contribute to capillary lumenal narrowing, increase of hydraulic resistance, and, thus, impairment of perfusion. Whether the postischemic diameter response with dilation of reperfused capillaries and lumenal narrowing of no-reflow capillaries involves endothelin/nitric oxide-triggered capillary pericyte function remains to be determined.