The open-ended microbial diagnostic approaches such as the complete or partial sequencing of the 16S ribosomal gene by Sanger sequencing or by pyrosequencing have provided new insights into the diversity of the oral microbiota. These techniques have recently been used to evaluate the microbiota associated with osseointegrated implants and these results have expanded the knowledge on the diversity of the microbial communities associated with peri-implantitis. Taken together, the results of these studies suggest that the diversity of the microbial community of peri-implantitis and periodontitis might not be as similar as previously thought. Although certain known periodontal pathogens may also be associated with the etiology of peri-implantitis, apparently there were many differences between these two clinical conditions, involving distinct microorganisms. Further investigations on the diversity of peri-implant microbiota would be essential in order to define effective preventive and therapeutic strategies for peri-implantitis. It is also important to standardize laboratory protocols to make the results of the open-ended diagnostic techniques based on PCR amplification more comparable throughout the different research groups.