Longitudinal studies have shown that successful implants are colonized by a predominantly Gram-positive, facultative flora, which is established shortly after implantation. Repeated microbiological sampling in patients with clinically stable implants showed no significant shifts in the composition of this flora over five years. In patients with bone loss and pocket formation around implants, however, a significantly different flora was found: Gram-negative anaerobic bacteria, particularly fusobacteria, spirochetes, and black-pigmenting organisms such as Prevotella intermedia were often present in high proportions. Antimicrobial treatment with agents specifically active against anaerobes could halt progression of peri-implant infections in such cases. Although there may be non-microbial primary causes for implant failure, these studies show that Gram-negative anaerobes may play a role in peri-implant infections, and that their elimination leads to improvement of the clinical condition.