Many important risk factors for oral cancer have been elucidated. Tobacco in its many forms is perhaps the most important risk factor, both because of its strong relationship with the disease and because of its high prevalence around the world. Alcohol use alone may elevate the risk of oral cancer, although its predominant effect comes from interaction with tobacco. The epidemiologic evidence supporting an increased risk for HPV type 16 is also unequivocal. A protective association with consumption of fruits and vegetables has been consistently shown, although it is difficult to make an interpretation due to the potential for confounding and bias. Finally, there appears to be a role for common genetic polymorphisms that by themselves may not substantially impact the disease risk, but that in concert with environmental exposures may lead to development of oral cancer. The majority of oral cancers that occur globally are attributed to causes that are for the most part modifiable.