Despite considerable advances in treatment development, cigarette smoking remains the leading cause of preventable death in the United States, and most smokers engaged in treatment are unsuccessful in quitting. The burden of illness is disproportionately borne by female smokers, who are less responsive to cessation interventions than males. The relationships between stress, craving, and smoking behavior are recognized as key factors underlying gender differences in nicotine dependence, but must be better understood and characterized to yield avenues for interventions addressing this critical health disparity.