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Systemic and oral health are interconnected via bacteria and their byproducts which can circulate throughout the body which are found in the oral biofilm. Oral biofilm and its associated periodontal health have not been frequently addressed in patients with systemic health issues. This is especially true for those patients who do not respond to medical treatment via their physician for systemic issues. The periodontal sulcus in the absence of clinical presence of periodontal disease (bleeding on probing, gingival inflammation) may have oral biofilm present. Periodontal reaction is dependent on the patient’s immune response to the associated bacteria and their byproducts present in the oral biofilm. Increasing evidence has emerged in recent years that are connecting oral biofilms with systemic conditions, either by initiating them or by complicating those medical conditions. Patient health needs to be considered as a whole-body system with connections that may originate in the oral cavity and have distant effects throughout the body. In order to maximize the patient’s total health, healthcare needs to be a coordination between the physician and dentist to eliminate the oral biofilm and aid in the prevention of systemic disease or minimize these effects to improve the overall patient health and their quality of life. Various systemic health areas have been associated with the bacteria in oral biofilms and their byproducts. Those include cardiovascular disease, chronic kidney disease, diabetes, pulmonary disease, prostate cancer, colon cancer, pancreatic cancer, pre-term pregnancy, erectile dysfunction, Alzheimer’s disease, and rheumatoid arthritis. This article will discuss oral biofilm, its systemic effects, and review the medical conditions associated with the oral systemic connection with an extensive review of the literature to aid in demonstrating the total body connection.