Cerebrovascular disease is a major burden to individuals and their communities worldwide. Stroke is one of the leading causes of death and disability, and the prevention and treatment of stroke can be improved with a better understanding of its causation. Cerebral small vessel disease (SVD) is a subset of cerebrovascular disease, and has an equally large impact on an individual's quality of life. Although many risk factors are involved, we propose that genetics has a significant role in the pathogenesis of SVD through a complex interplay of environmental and multigenetic factors. Advances in molecular technology have enabled the human genome to be investigated both at a population and, more recently, an individual level. A better understanding of the molecular basis of SVD will enable the development of therapies to help in its prevention and treatment. This review assesses the molecular genetics underlying cerebral SVD.