Anatomy, physiology, and pathophysiology are inextricably linked in patients with intracranial atherosclerosis. Knowledge of abnormal or pathological conditions such as intracranial atherosclerosis stems from detailed recognition of the normal pattern of vascular anatomy. The vascular anatomy of the intracranial arteries, both at the level of the vessel wall and as a larger structure or conduit, is a reflection of physiology over time, from in utero stages through adult life. The unique characteristics of arteries at the base of the brain may help our understanding of atherosclerotic lesions that tend to afflict specific arterial segments. Although much of the knowledge regarding intracranial arteries originates from pathology and angiography series over several centuries, evolving noninvasive techniques have rapidly expanded our perspective. As each imaging modality provides a depiction that combines anatomy and flow physiology, it is important to interpret each image with a solid understanding of typical arterial anatomy and corresponding collateral routes. Compensatory collateral perfusion and downstream flow status have recently emerged as pivotal variables in the clinical management of patients with atherosclerosis. Ongoing studies that illustrate the anatomy and pathophysiology of these proximal arterial segments across modalities will help refine our knowledge of the interplay between vascular anatomy and cerebral blood flow. Future studies may help elucidate pivotal arterial factors far beyond the degree of stenosis, examining downstream influences on cerebral perfusion, artery-to-artery thromboembolic potential, amenability to endovascular therapies and stent conformation, and the propensity for restenosis due to biophysical factors.