Previous studies have found gender differences in the dynamics of tobacco smoking and cessation in humans. However the physiological basis for these differences is a subject of much debate. Animal studies have also revealed some gender-dependant differences in the neuropharmacological actions of acute and chronic nicotine. The purpose of this article is to review the clinical and basic science studies that have evaluated sex differences in tobacco use/cessation and the animal literature that has provided some clues regarding the possible underlying basis for these differences. The acute and chronic actions of ovarian steroid hormones on nicotinic receptors could play a direct or indirect role in mediation of gender differences in tobacco use dynamics, however no clear picture has emerged from these studies. The literature supports a general consensus women have a more difficult time with smoking cessation and that perhaps nicotine replacement therapy is less efficacious in female smokers. This could be due to alterations in nicotine pharmacokinetics mediated by estrogen, ovarian hormones acting as non-competitive nicotinic receptor antagonists, or many additional issues. Many studies assume that individuals, regardless of gender, have the same motivation for tobacco use and/or cessation. Individual reasons for smoking may simply override gender differences in the pharmacodynamic/pharmacokinetic actions of nicotine. Many animal studies that have reported gender differences in nicotine sensitivity have not carefully controlled for phase of the estrus cycle, and the results of preclinical studies do not always support conclusions that have been drawn from human studies. Thus there are still many questions that remain to be answered in this important area of research.