The cerebellum not only modulates the systemic circulation, but also profoundly influences cerebral blood flow (rCBF) and metabolism (rCGU), and initiates long-term protection of the brain from ischemia. Electrical stimulation of the rostral ventral pole of the fastigial nucleus (FN), elevates arterial pressure (AP), releases vasoactive hormones, elicits consummatory behavioral and other autonomic events and site specifically elevates rCBF independently of changes in rCGU. Cerebral vasodilation results from the antidromic excitation of axons of brain stem neurons which innervate cerebellum and, through their collaterals, neurons in the rostral ventrolateral reticular nucleus (RVL). RVL neurons initiate cerebral vasodilation over polysynaptic vasodilator pathways which engage a population of vasodilator neurons in the cerebral cortex. In contrast, intrinsic neurons of FN, when excited, elicit widespread reductions in rCGU and, secondarily, rCBF, along with sympathetic inhibition. Electrical stimulation of FN can reduce the volume of a focal cerebral infarction produced by occlusion of the middle cerebral artery by 50%. This central neurogenic neuroprotection is long lasting (weeks) and is not due to changes in rCBF or rCGU. Rather, it appears to reflect alterations in neuronal excitability and/or downregulation of inflammatory responses in cerebral vessels. The FN, therefore, appears to be involved in widespread autonomic, metabolic, and behavioral control, independent of motor control. The findings imply that the FN receives inputs from neurons, probably widely represented in the central autonomic core, which may provide continuing information processing of autonomic and behavioral states. The cerebellum may also widely modulate the state of cortical reactivity to ischemia, hypoxia, and possibly other neurodegenerative events.