This article questions several assumptions about the rationale for pharmacological therapies for smoking cessation, including whether (a) future smokers will be those more dependent on nicotine and thus in greater need of nicotine replacement or other pharmacotherapy, (b) transdermal nicotine and nicotine gum work by reducing withdrawal symptoms, and (c) clonidine works by decreasing sympathetic arousal. After describing currently available pharmacotherapies, the article also describes several unexpected findings that need to be taken into consideration by clinicians: (a) transdermal nicotine is effective when given without psychological therapy, (b) transdermal nicotine and nicotine gum do not consistently decrease postcessation weight gain, (c) high level of nicotine dependence does not consistently predict better response to transdermal nicotine, and (d) clonidine is effective in women but not in men. The article poses other questions for future research.