Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a major hereditary small vessel disease caused by mutations in NOTCH3. The variations in progression and severity among patients suggest that the CADASIL phenotype is modified by some genetic and environmental factors. The gene discussed is NOTCH3; the disease is cerebral arteriopathy with subcortical infarcts and leukoencephalopathy.