 Due to the ability of the blood-brain barrier, BBB, to prevent the entry of drugs into the brain, it is a challenge to treat central nervous system disorders pharmacologically. The development of nanotechnology provides potential to overcome this problem. In this review, the barriers to brain-targeted drug delivery are reviewed, including the BBB, blood-brain tumor barrier, BBTB, and nose-to-brain barrier. Delivery strategies are focused on overcoming the BBB, directly targeting disease cells in the brain, and dual-targeted delivery. The major concerns and perspectives on constructing brain-targeted delivery systems are discussed.