The vascular abnormalities that arise during sepsis imply disturbances in the delicately tuned homeostatic mechanisms of vascular endothelium and smooth muscle. In the microvasculature, smooth muscle tone represents a complex equilibrium among metabolic stimuli, hemodynamic forces, and neurohumoral influences. Local tissue perfusion also is modulated by vasoactive mediators that can be produced locally, through endothelium-dependent adhesion and activation of inflammatory cells, or at a distance. In sepsis, derangement of normal autoregulation of perfusion, together with toxic effects of mediators, may be severe enough to result in organ dysfunction. Recent advances in vascular biology have illuminated a variety of targets, such as adhesion molecules, platelet activating factor, and inducible nitric oxide synthase for potential therapeutic intervention in sepsis.