The thermoregulatory control of human skin blood flow is vital to the maintenance of normal body temperatures during challenges to thermal homeostasis. Sympathetic neural control of skin blood flow includes the noradrenergic vasoconstrictor system and a sympathetic active vasodilator system, the latter of which is responsible for 80% to 90% of the substantial cutaneous vasodilation that occurs with whole body heat stress. With body heating, the magnitude of skin vasodilation is striking: skin blood flow can reach 6 to 8 L/min during hyperthermia. Cutaneous sympathetic vasoconstrictor and vasodilator systems also participate in baroreflex control of blood pressure; this is particularly important during heat stress, when such a large percentage of cardiac output is directed to the skin. Local thermal control of cutaneous blood vessels also contributes importantly--local warming of the skin can cause maximal vasodilation in healthy humans and includes roles for both local sensory nerves and nitric oxide. Local cooling of the skin can decrease skin blood flow to minimal levels. During menopause, changes in reproductive hormone levels substantially alter thermoregulatory control of skin blood flow. This altered control might contribute to the occurrence of hot flashes. In type 2 diabetes mellitus, the ability of skin blood vessels to dilate is impaired. This impaired vasodilation likely contributes to the increased risk of heat illness in this patient population during exposure to elevated ambient temperatures. Raynaud phenomenon and erythromelalgia represent cutaneous microvascular disorders whose pathophysiology appears to relate to disorders of local and/or reflex thermoregulatory control of the skin circulation.