Smoking rates have declined in recent years less rapidly in women than in men. More adolescent girls than boys are currently smoking. Quitting smoking is reported in many studies to be more difficult in women than in men. These observations suggest that there may be gender differences in the nature of nicotine addiction. Gender differences in various pharmacological processes involved in nicotine addiction are reviewed. Women take in less nicotine from smoking per cigarette than men but, because of slower metabolism, nicotine levels in the body for a given number of cigarettes per day are similar in male and female smokers. Women tend to be less sensitive to the discriminative effects of nicotine and tend to regulate nicotine intake less precisely than men. On the other hand, women appear to be more sensitive to the effects of nicotine in reducing negative affect and reducing body weight. There is a strong association between depression and smoking, and this association appears to be stronger in women than in men. Women tend to respond more to environmental cues associated with smoking than do men. Thus, several lines of evidence suggest that nicotine addiction is different in women than in men. Understanding the basis for gender differences may be of utility in individualizing and optimizing smoking cessation therapy.