Purpose: To verify whether the diversity of systemic medical conditions and smoking act as biologic associated factors for peri-implantitis. Materials and Methods: The PICO question was: "In patients with osseointegrated dental implants, does the presence of smoking habits or a compromised medical status influence the occurrence of peri-implantitis compared with the presence of good general health?" Smoking and systemic conditions such as type 2 diabetes mellitus, cardiovascular diseases, rheumatoid arthritis, lung diseases, obesity, cancer, deep depression, and osteoporosis were screened. Selection criteria included at least 10 patients per condition, 1 year of follow-up after implant loading, and strict cutoff levels (probing pocket depth [PPD], bleeding on probing [BOP] and/or pus, marginal bone loss) to define peri-implantitis. Results: From the 1,136 records initially retrieved, 57 were selected after title and abstract analyses. However, only six papers were considered for qualitative evaluation. No randomized controlled clinical trial was found. Smoking was associated with peri-implantitis in only one out of four studies. Poorly controlled type 2 diabetes accentuated only PPD and radiographic marginal bone level prevalence rates in peri-implant patients (one study). Cardiovascular disease was considered a risk (one out of two studies). The chance of peri-implant patients harboring the Epstein-Barr virus was threefold in one report. No associations were found for rheumatoid arthritis. Conclusion: Data from existing studies point to smoking and diabetes as biologic associated factors for peri-implantitis. However, the body of evidence is still immature, and the specific contribution of general health problems to peri-implantitis requires additional robust epidemiologic and clinical investigations. Keywords: biologic factors, dental implants, peri-implantitis, systemic diseases