Central nervous system (CNS) diseases are some of the most difficult to treat because the blood-brain barrier (BBB) almost entirely limits the passage of many therapeutic drugs into the CNS. Gene therapy based on the adeno-associated virus (AAV) vector has the potential to overcome this problem. For example, an AAV serotype AAV9 has been widely studied for its ability to cross the BBB to transduce astrocytes, but its efficiency is limited. The emergence of AAV directed evolution technology provides a solution, and the variants derived from AAV9 directed evolution have been shown to have significantly higher crossing efficiency than AAV9. However, the mechanisms by which AAV crosses the BBB are still unclear. In this review, we focus on recent advances in crossing the blood-brain barrier with AAV vectors. We first review the AAV serotypes that can be applied to treating CNS diseases. Recent progress in possible AAV crossing the BBB and transduction mechanisms are then summarized. Finally, the methods to improve the AAV transduction efficiency are discussed.