Smoking is responsible for approximately one in five deaths in the United States per year. The Surgeon General's 1964 report first linked smoking as a cause of cancer. Since then cigarette smoking has had a steady decline to its current estimate of 19.8%. There are, however, some special populations where smoking continues to occur at a higher prevalence than the general population. This chapter discusses tobacco dependence among the following special populations: low socioeconomic status including Medicaid, hard-core smokers, rural, and homeless; immigrants; and persons living with HIV. For each population, there is an overview of the disparities in tobacco use, special challenges unique to that population, and exploration of current research on tailoring of tobacco dependence treatment. Each of the special populations discussed present unique challenges with tobacco dependence treatment that will require careful examination before disparities will ultimately decrease. Eliminating disparities has been marked as an important research agenda item as noted in Healthy People 2010. Nurse researchers are well positioned to combine their clinical expertise and knowledge of patient psychosocial needs with investigation of patient-focused research questions in each of these special populations.