Smoking is a well-established risk factor for cardiovascular disease (CVD). This chapter provides an overview of a program of nursing research relevant to tobacco use in patients with CVD. The Women's Initiative for Nonsmoking (WINS) provides a rich demonstration of a key randomized clinical trial (RCT) on the efficacy of smoking cessation in women. The National Institutes of Health priority for data mining of existing RCTs is demonstrated in the numerous presentations of findings from secondary papers from WINS that answer additional research questions relevant to smoking cessation, including the influence of depression on smoking, myths about and underuse of nicotine replacement therapy. The methodological and logistical challenges inherent in tobacco intervention studies are presented, including a discussion of research needed in the measurement of withdrawal symptoms. Additionally, the role and contributions of nurses serving on the federal guideline development process are highlighted. International research activities of the coauthors from Jordan and Korea are also presented, including a discussion of the need for research in waterpipe use.