The retroviral phenomenon of superinfection resistance defines an interference mechanism that is established after primary infection, and provides possible protection against the challenge with the same virus. A better knowledge of superinfection resistance-induced mechanisms could be useful for the development of an HIV vaccine or other antiviral strategies. Present studies suggest that the SIR based on infected cells and the immune response in vivo were concluded to be the main possible reasons for the protection against superinfection. However, so far the real mechanism in protecting patients from HIV superinfection has not been studied throughly. This paper reviews the findings and introduces the updates of superinfection with HIV infection.