Prevention is particularly challenging in implant-associated bone and joint infection, as it could reduce the following: (1) the risk of infection in particular patient populations; (2) the risk associated with particular surgical procedures; and/or (3) the risk of infection with particular pathogen that has the ability to produce biofilm, such as staphylococci. As a consequence, it is crucial to identify: (1) host-related risk factors that may be involved in the acquisition of infection; (2) surgical procedures particularly at risk of infection; and (3) the different ways to target the most frequent pathogens involved in implant-associated spinal infection. In this article, we reviewed the data of the literature on the infection prevention in spine surgery.