Persons who use chewing tobacco and snuff experience an increased risk of oral cancer. Because of the pharmacologic properties of nicotine and other constituents of smokeless tobacco, there is also concern that smokeless tobacco products may lead to cardiovascular diseases as well. The relatively few human population studies to date conflict with respect to whether smokeless tobacco use elevates cardiovascular risk factors or leads to cardiovascular disease or death from cardiovascular causes. Hemoglobin adducts to carcinogens present in smokeless tobacco products are measurable in the blood of smokeless tobacco users, indicating that smokeless-tobacco-related carcinogens circulate throughout the body. This prompts a concern that smokeless tobacco may increase risks of other cancers as well. The evidence to date from epidemiologic studies indicates no relationship between smokeless tobacco and bladder cancer, but there is suggestive evidence linking smokeless tobacco use to prostate cancer risk. Only single studies have been conducted of some cancers, and inconsistencies among studies of the same cancer site have been reported. Molecular epidemiologic studies may help identify markers of malignant transformation in smokeless tobacco users that may help in early intervention to prevent or ameliorate the consequences of oral cancer. Further studies are needed to determine more clearly the cardiovascular and non-oral cancer risks potentially associated with smokeless tobacco use.