Recombinant adenovirus-associated virus (rAAV) vectors mediated gene delivery system has been widely used in the treatments of cancer or other genetic diseases. It is considered to be one of the most promising vector owing to its non-pathogenicicity, low immune response, potential to integrate site-specif-ically, persistent and stable gene expression. However, it was limited in clinical applications because it is easy to be neutralized in serum and non-selection to the target site. Chemical modifications of rAAV have been studied to overcome those problems. This article reviewed the progress of chemical modifications of rAAV by various compounds and different modification methods, and predicted what the researches needed to do in the future.