This article explores possible historical and cultural reasons for the high prevalence of contemporary tobacco use among North American Indian populations. A literature review of American Indian tobacco use in early precontact and colonial times reveals that tobacco was used extensively for ceremonial, spiritual, social, political, and medicinal purposes. Centuries of aboriginal sacred use of tobacco, combined with increasing commercial use since the fur trade, may have provided a residual base of susceptibility for later secular use-an old form with a new meaning. Because of its high prevalence rate among most American Indian social groupings, tobacco is very probably the greatest threat to the health of American Indians today. Its addictive qualities place it on a par with alcohol as a source of physical and psychological dependency, a fact not always recognized in American Indian social contexts.