Peri-implant diseases have been recognized to significantly impact the outcome of dental implantation procedures and thus catch more and more attention. Although the role of bacterial infection in initiating peri-implantitis is disputed, the generally present consensus is that peri-implantitis is caused by microorganisms present in the oral environment and subsequent biofilm build-up. This chapter reviews the previously identified predominant species of the microorganisms, including bacteria, virus, and fungi, that contribute to implant surface biofilm formation. In addition, to provide a comprehensive review, the current knowledge on the novel diagnosis, prevention, and treatment of peri-implantitis related pathogens, as well as currently available peri-implantitis models for assessing the interactions among dental implant surface, biofilm, and host immune system are discussed in the current chapter.