This chapter discusses the utility of single-photon emission computed tomography (SPECT) in the evaluation of carotid disease and interventions. A prospective study demonstrated that reduced regional cerebrovascular reactivity (rCVR) to acetazolamide determined quantitatively using 133Xe SPECT is significantly associated with an increased risk of stroke recurrence in patients with symptomatic occlusion of the middle cerebral artery (MCA) or internal carotid artery. Post-operative hyperperfusion is observed only in patients with reduced preoperative cerebrovascular reactivity to acetazolamide. Preoperative assessment of cerebral blood flow (CBF) with acetazolamide challenge using SPECT can identify patients at risk for postcarotid endarterectomy hyperperfusion. A SPECT study performed between the first and third post-operative day could be advocated for the timely and reliable identification of patients at risk for hyperperfusion syndrome. CBF measurements can determine appropriate withdrawal of blood pressure control in patients with ischemic events related to other atherosclerotic steno-occlusive lesions.