Purpose: To identify the most effective interventions for treating peri-implantitis around osseointegrated oral implants. Materials and methods: The Cochrane Oral Health Group's Trials Register, CENTRAL, MEDLINE and EMBASE were searched up to the 9th of June 2011 for randomised controlled trials (RCTs) comparing agents or interventions for treating peri-implantitis around oral implants. Primary outcome measures were implant failure, radiographic marginal bone level change, complications and side effects, and recurrence of peri-implantitis. Screening of eligible studies, assessment of the methodological quality of the trials and data extraction were conducted in duplicate and independently by two review authors. The statistical unit was the patient and not the implant unless the clustering of the implants within the patients had been taken into account. Results were expressed as random-effects models using mean differences for continuous outcomes and risk ratios for dichotomous outcomes with 95% confidence intervals (CI). Results: Fifteen eligible trials were identified, but six were excluded. The following interventions were compared in the nine included studies: different non-surgical interventions (five trials), adjunctive treatments to non-surgical interventions (one trial), and different surgical interventions (two trials) and adjunctive treatments to surgical interventions (one trial). Follow-up ranged from 3 months to 4 years. No study was judged to be at low risk of bias. Statistically significant differences were observed in two small single trials judged to be at unclear or high risk of bias. After 4 months, adjunctive local antibiotics to manual debridement in patients who lost at least 50% of the bone around implants showed improved mean probing attachment levels (PAL) of 0.61 mm (95% CI 0.40 to 0.82) and reduced probing pockets depths (PPD) of 0.59 mm (95% CI 0.39 to 0.79). After 4 years, patients with peri-implant infrabony defects >3 mm treated with Bio-Oss and resorbable barriers showed an improvement of 1.4 mm for PAL (95% CI 0.24 to 2.56) and PPD (95% CI 0.81 to 1.99) compared to patients treated with a nanocrystalline hydroxyapatite. Conclusions: There is no reliable evidence suggesting which could be the most effective interventions for treating peri-implantitis. This is not to say that currently used interventions are not effective. A single small trial at unclear risk of bias showed that the use of local antibiotics in addition to manual subgingival debridement was associated with a 0.6 mm additional improvement in PAL and PPD over a 4-month period in patients affected by severe forms of peri-implantitis. Another small single trial at high risk of bias showed that after 4 years, improved PAL and PPD of about 1.4 mm were obtained when using Bio-Oss with resorbable barriers compared to a nanocrystalline hydroxyapatite in peri-implant infrabony defects. There is no evidence from four trials that the more complex and expensive therapies were more beneficial than the control therapies, which basically consisted of simple subgingival mechanical debridement. Follow-up longer than 1 year suggested recurrence of peri-implantitis in up to 100% of the treated cases for some of the tested interventions. As this can be a chronic disease, re-treatment may be necessary. Larger well-designed RCTs with follow-ups longer than 1 year are needed.