This article reports on the recent growth of transnational tobacco companies (TTCs) in South America. Although some scholarly attention has been directed toward such growth in Asia and eastern Europe, South America has also been targeted by TTCs’ aggressive expansionist practices in recent years. Fighting “Big Tobacco” is entirely different from combating most public health problems. Unlike cigarettes, most infectious diseases and maternal and child health problems never provide profits to transnational corporations and governments. Also, most public health problems (with alcohol being another notable exception) are not exacerbated by extensive advertising campaigns that promote the cause of the health problems. Supported by data gathered during three months of fieldwork in Ecuador, Peru, Chile, and Argentina in 1997, this article suggests that the TTCs’ marketing strategies override cultural differences in the choices people make regarding smoking and health. Combining critical medical anthropology and public health, this article concludes that unless dramatic actions are taken, an avoidable outbreak of tobacco related diseases will eventually reach epidemic proportions on the South American continent. It is also a “call to arms” for more medical anthropologists to investigate tobacco-related matters around the world.