Within the intracranial vasculature, atherosclerosis occurs in two distinctive patterns: (1) in Western populations who have severe extracranial and systemic atherosclerosis, the severity of intracranial involvement is consistently less than that within extracranial arteries; and (2) in Asians, Africans, and Hispanics, who often have isolated intracranial arterial disease that is found to be more often accompanied by brain infarction than comparable extracranial atherosclerotic disease. Compared to coronary and extracranial carotid atherosclerosis, intracranial atherosclerosis has distinct pathological characteristics compared to that of extracranial arteries. Intracranial atherosclerosis (ICAS) had been understudied due to the relative inaccessibility of cerebral artery specimens under current treatment strategies. Acquiring post-mortem cerebral vessel specimens for histology processing is the most direct method to analyze the pathological characteristics of ICAS, in order to analyze both lumen stenosis and plaque components contributing to brain infarctions. The developments in high resolution magnetic resonance imaging (HRMRI) make it feasible to assess human ICAS in vivo. It is nevertheless challenging to understand vessel wall changes within brain vasculature demonstrated on HRMRI, as well as to identify biomarkers for stroke risk stratification and treatment strategy modification. Knowledge about intracranial atherosclerosis remains limited due to lack of human arterial specimens, and the development of proper animal models of human cerebral atherosclerosis is necessary to explore the pathogenesis of intracranial atherosclerosis and to assess various strategies preventing or treating ICAS-related stroke.