Moyamoya disease is a chronic occlusive cerebrovascular disease with unknown etiology characterized by bilateral steno-occlusive changes at the terminal portion of the internal carotid artery (ICA), associated with abnormal vascular networks at the base of the brain. Recent genetic research suggests that the RNF213 gene located at chromosome 17q25 may be the susceptibility gene for moyamoya disease. RNF213 mutation predicts both early-onset and the severe form of moyamoya disease. As secondary insults in addition to the genetic abnor-mality, autoimmune response, inflammation/infection, radiation, and endothelial progenitor cells may together be implicated in the etiology of moyamoya disease. Finally, the dynamic nature of moyamoya disease, which is the self- compensatory reorganization system demonstrating the conversion of the blood flow supply from ICA system to the external carotid artery system, should be clarified to understand the pathophysiology of moyamoya disease.