The toll of tobacco use on a pulmonary practice is severe. Physicians, patients, and their families experience frustration, hopelessness, and even anger when confronted with a seemingly irrational decision to keep smoking despite morbid lung disease. This paper examines the biological basis of this behavior and seeks to integrate this insight into a rational approach to the problem in practice. Smoking is reexamined within the framework of an irrational compulsion to seek nicotine, despite a rational desire to stop. Control over the compulsion to smoke is established as an important clinical outcome, and the rationale for treating tobacco dependence as a chronic illness is examined. Finally, practical insights into managing ambivalence, including an aggressive pharmacotherapeutic approach based on the neurobiology, are presented.