The central nervous system (CNS) is vascularized by a dense capillary network that is critical to deliver oxygen and nutrients, and remove carbon dioxide and waste products, from the neural tissue. These blood vessels contain a series of properties, termed the blood-brain barrier (BBB), which distinguishes them from vasculature in other tissues, enabling CNS vessels to stringently regulate the transfer of ions, molecules and cells between the blood and the tissue. This barrier is critical to maintain brain homeostasis which allows for proper neuronal function and also to protect the tissue from injury and disease and many neurological diseases are associated with BBB dysfunction, including traumatic brain injuries, Alzheimer's disease, stroke, epilepsy, and multiple sclerosis. Therefore, a better understanding of the mechanisms controlling the development of the BBB may lead to improved comprehension of the pathophysiology of these diseases, and further aid in the identification of targets to modulate the barrier to treat different neurological diseases. Many of the properties of the BBB are possessed by the endothelial cells that form the walls of the blood vessels but are acquired through a series of complex cellular interactions with the microenvironment throughout its development. We will review what is known about the induction and regulation of BBB properties during development.