The vasculature of the central nervous system (CNS) is highly specialized with a blood-brain-barrier, reciprocal neuroepithelial-endothelial cell interactions and extensive pericyte coverage. Developmentally, numerous important signaling pathways participate in CNS angiogenesis to orchestrate the precise timing and spatial arrangement of the complex CNS vascular network. From a therapeutic standpoint, the CNS vasculature has attracted increased attention since many human ailments, such as stroke, retinopathy, cancer and autoimmune disease are intimately associated with the biology of CNS blood vessels. This review focuses on growth factor pathways that have been shown to be important in developmental CNS vascularization through studies of mouse genetic models and human diseases.