Since 1990 when Wolff and co-authors proved that both RNA and DNA expression vectors containing interest gene were directly injected into mouse muscle and expressed the protein in vivo, the concept of gene vaccine has been broadly tested in the vaccine field. However, due to the limitations of technology and the misconception about RNA, most previous studies have focused on the DNA vaccine. Recently, the RNA vaccine has emerged as a new game-changing disruptive innovation technology in the vaccine field. This review has covered the characteristics of the RNA vaccine, including its strengths and weaknesses. Finally, we have suggested future directions for the RNA vaccine.