The cerebral small vessel disease (CSVD) refers to a group of pathological condition that affects the intracranial small vessels. CSVD causes lacunar infarction, white matter disease and hemorrhage, and may contribute to development of dementia and motor disability in the elderly. CSVD is a common aging phenomenon, however, little is known about its molecular pathogenesis. To understand the molecular pathogenesis for CSVD, here, we review the clinical spectrum, pathological findings and the molecular pathogenesis of CSVD caused by single gene defect: including cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy, cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy, COLAA1-related disorders, retinal vasculopathy with cerebral leukodystrophy, Fabry disease, and hereditary cerebral amyloid angiopathy.