The cost of smoking has been explored for residents of the U.S. living in several states. Recent evidence has indicated that the prevalence and cost of smoking are associated with racial and ethnic groups. This study provides information on tobacco prevention and control for American Indians (AI) (American Indians refers to American Indians and Alaska Natives throughout this article. Where we use the term California tribe we specifically mean persons who are members of Indigenous tribes geographically located in the geographic area now known as the state of California.) and examines the relative impact of smoking by using behavioral and demographic characteristics in order to predict the economic cost on AIs. The analysis suggests that AIs smoke more frequently than other Californians, which results in higher health care costs, as well as morbidity and mortality due to high levels of tobacco related chronic disease. Based on these factors we urge tribes to exercise their sovereignty as governments and implement local tobacco control policy strategies. We call for public health action by community leaders in Indian country and nationwide. We must act now to protect future generations.