Cigarette smoking continues to place an enormous burden on US health systems. The treatment of tobacco-dependent persons is vital to the public health, since unmitigated smoking could lead to the development of disease and premature death in as many as 20 million current smokers in the United States. Much of this tobacco-related morbidity and mortality could be prevented by the application of existing treatments, as well as newer ones. Access to safe and effective treatments was significantly expanded in 1996, when two forms of nicotine replacement therapy (NRT), the nicotine gum and patch, became available for over-the-counter sale. Expanded access has led to significantly increased utilization and quitting. Even with these advances, however, the scope of this tobacco dependence demands that we explore alternative treatment strategies, including exposure reduction therapy (ERT) as a possible option for smokers not currently making quit attempts. In this review, we present principles to guide the development of such a therapy, and for its application, should it be proven effective.