Smokeless tobacco has been associated with oral cancer for many decades. The purpose of this article is to review research relevant to this association, including epidemiologic studies, studies of putative carcinogens such as tobacco-specific nitrosamines (TSNAs) and other contaminants, and possible cancer inhibitors. Epidemiologic studies addressing this issue primarily consist of case-control studies. They show that the use of chewing tobacco and moist snuff is associated with very low risks for cancers of the oral cavity and related structures (relative risks [RR] from 0.6 to 1.7). The use of dry snuff is associated with higher RRs, ranging from 4 to 13, while the RRs from smokeless tobacco, unspecified as to type, are intermediate (RR = 1.5 to 2.8). With regard to TSNAs, historical levels in American moist snuff products were higher than those in their Swedish counterparts, but levels in contemporary products are uniformly low. TSNA levels in chewing tobacco have always been low, but levels in dry snuff have been higher, including some very high levels in current products. In general, smokeless tobacco users are not exposed to significant levels of cadmium, lead, benzo(a)pyrene, polonium-210, and formaldehyde, when compared with concentrations of these compounds in foods. Finally, low oral cancer risk from smokeless tobacco use may be influenced by the presence of cancer inhibitors, mainly anti-oxidants, in smokeless tobacco products.