Blood vessels in the nervous system have traditionally been considered neutral bystanders that only passively adapt their structure and function in response to the needs of neural cells. Emerging evidence suggests, however, that vessels and angiogenic molecules actively participate in the pathogenesis of neurological disorders. Here we will discuss molecular insights into neurological disorders resulting either from excessive vessel growth (cerebral vascular malformations) or improper vessel regression (neurodegeneration and white matter lesions). These genetic insights offer alternative therapeutic options, some of which are being evaluated in the clinic.