Atherosclerosis, regardless of the arterial location, shares common features of intimal smooth muscle cells, inflammation, thrombosis, and extracellular accumulation of matrix, lipid, and calcification. This chapter characterizes atherosclerotic carotid disease in light of our knowledge of coronary atherosclerosis, and relates carotid plaque morphology to cerebral ischemic syndromes with special focus on features of plaque instability. It is difficult to correlate carotid, aortic and cerebrovascular plaque morphology at autopsy, for technical reasons. High flow rates and the shear forces caused by the bifurcation of the common carotid artery into the internal and external carotids result in unique features of carotid plaque morphology as compared to the coronary circulation. The reduction of stroke risk after carotid endarterectomy is attributed to removal of the cerebral embolic source in most patients. The chapter also provides a comparison of the histomorphometric features of unstable coronary and carotid atherosclerotic plaques.