(1) Cerebral protection devices offer a new approach to reducing the risk of stroke and death in patients undergoing carotid angioplasty with stenting (CAS). (2) Nine studies have examined the efficacy of cerebral protection devices, by comparing the incidence of procedure related stroke and death to that of CAS without protection, and to surgical endarterectomy. Few of the studies were of high quality. (3) Overall, the differences in the incidence of procedure-related stroke and death were not statistically significant among patients who underwent CAS without protection, compared to those who received CAS with protection, or to those who underwent endarterectomy. (4) Complications reported with the use of cerebral protection devices are minor and transient. (5) CAS with cerebral protection may offer a safe and efficacious alternative to endartectomy in symptomatic, high risk patients with severe carotid artery disease. Evidence to support the use of CAS with cerebral protection devices in asymptomatic patients who have severe carotid artery stenosis, is unavailable.