This article reviews the literature to compare differential outcomes among men and women after smoking cessation, assess barriers they may face during cessation and provide recommendation to address gender-specific challenges in smoking cessation interventions. There is some evidence that women achieve lower abstinence rates than men after a quit attempt with nicotine replacement therapy, as well as without pharmacotherapy, and several underlying mechanisms were discussed to account for these findings. These include: (a) women have specific genetic variants that affect pharmacokinetics and pharmacodynamics of the medication, (b) hormonal influences increase nicotine metabolism and withdrawal symptoms, (c) women are more responsive to nonpharmacological aspects of smoking than men, (d) women are more vulnerable to depression and negative mood than men, (e) weight concerns are greater barriers for women than for men and (g) women receive less effective social support than men during a quit attempt. Gender-specific counselling that accounts for these factors and addresses the different needs of men and women may be a promising approach to improve long-term abstinence rates. However, more research is required to identify gender-related underlying mechanisms of differential smoking cessation outcomes, develop tailored interventions that account for gender differences and study the implementation and outcomes of gender-responsive treatment approaches.