The control of skeletal muscle resistance vessel tone is critical for 1) the regulation of muscle tissue oxygenation to support continued metabolic and contractile activity, and 2) regulation of arterial blood pressure. With regard to muscle oxygenation, vasodilatation is often capable of a remarkably tight matching of increases in muscle blood flow (oxygen delivery) with increases in metabolic demand. Rapid onset vasodilator mechanisms likely related to muscle activation and mechanical distortion can initiate increases in muscle blood flow with the first contraction of exercise. This initial response can be complete within 5-10 seconds and often, though not always, constitutes the majority of the blood flow increase with exercise. Slower onset “feedback” mechanisms related to muscle metabolism and oxygenation are thought to achieve final matching of muscle blood flow to metabolic demand. This matching can be uncoupled however, since exercising muscle blood flow does not recover to steady state levels when local perfusion pressure is altered. With regard to blood pressure regulation, the capacity of skeletal muscle to increase metabolic activity far surpasses that of any other tissue. The muscle blood flow required to match this demand can challenge and even surpass the pumping capacity of the heart. Given that the arterial baroreflex is reset to higher levels with increasing exercise intensity and relies primarily on vasoconstriction in regulating blood pressure, this necessitates that muscle resistance vessels become a critical target for sympathetic neural vasoconstriction as part of arterial blood pressure regulation. Therefore, control of skeletal muscle resistance vessels in exercise integrates the competing requirements for regulation of muscle oxygenation and regulation of arterial blood pressure. While arterial blood pressure ultimately takes precedence, local factors in exercising muscle can reduce responsiveness to sympathetic vasoconstriction in accordance with local metabolic demand. This is known as “functional” sympatholysis. Current concepts propose that this may optimize the balance between vasoconstrictor and vasodilator influences across exercising muscles. The result is that sympathetic neural restraint of exercising muscle blood flow is minimized while arterial blood pressure regulation is maintained.