Abstract Objectives Periodontal disease has long been linked to many systemic diseases, and recently a link between periodontal disease and cancer has been established. The purpose of this paper is to review the literature to explore the evidence to date of a relationship between periodontal disease and cancer. In addition, the main hypotheses for the association are discussed along with challenges in evaluating the evidence. Data/sources/study selection In this review, English-language papers studying the relationship between periodontal disease or tooth loss in humans and increased risk of several types of cancers along with overall cancer risk between 1990 and April 2009 were reviewed. Conclusions The most consistent increased risk was noted in studies of oral and esophageal cancers and periodontal disease. Gastric and pancreatic cancers had an association in most but not all studies. Lung, prostate, hematologic and other cancers were less consistently associated or did not have sufficient studies to determine a predictable pattern. Studies to date indicate a positive correlation between several forms of cancer and periodontal disease.