The aim of this systematic review was to assess the treatment of peri-implantitis with special emphasis on the role of anti-infective therapy. No randomized controlled clinical trial was available for analysis. Of 145 peri-implant studies initially screened, 21 studies (six human and 15 animal studies) were analysed regarding the outcome of treatment of peri-implantitis. A multitude of treatment regimens, including anti-infective therapy, was reported. The antibiotic regimens varied between studies. No standardized medication protocol was used. Type of antibiotic, dosage, duration and time for initiation of antibiotic treatment were different for all studies, but details were not always reported. A non-medicated control group was reported in one animal experiment only. The outcomes following anti-infective treatment of peri-implantitis are highly variable. The evidence for a consistent and clinically relevant advantage using antibiotics can be questioned in this context. There are to date no data available to support specific treatment protocols. It is suggested that randomized human controlled clinical trials for the treatment of peri-implantitis be initiated.