Delivering drug to the brain has still many obstacles. Especially crossing the brain barriers is a big challenge. The application of nanomaterials to medicine has provided the development of novel drug carriers, can facilitate the delivery of drugs to the brain. Niosomes are non-ionic surfactant based vesicles and has been used as a nanocarrier for different types of drugs. Moreover, niosome surfaces can be modified with targeting ligands to enable cell-specific targeting. Because of these promising features, niosomes have a great potential using as a carrier for the delivery of drugs to the brain. The present chapter provides the fundamental information about niosomal drug delivery systems and their recent applications brain targeting.