The post-partum period represents an ideal opportunity to promote smoking cessations given that: 1) many women have stopped smoking during pregnancy, motivated to improve fetal outcomes; and, 2) smoking relapse appears at a very discrete time-point, giving an optimal time to deliver an intervention. Unfortunately, the post-partum period also offers some unique challenges. First, the most effective strategy to prevent relapse appears to be prolonged pharmacotherapy. Given the safety concerns and lack of efficacy of these agents in pregnancy, most women who quit smoking have done so without the use of pharmacologic agents as these agents are not routinely recommended nor utilized in clinical practice. There is no evidence to support the efficacy of behavioral interventions to prevent relapse in non-pregnant adults and to date, prior studies of behavior interventions in the post-partum period have been largely null at preventing relapses. Finally, all current FDA-approved smoking cessations pharmacologic therapies are excreted into breast milk and manufactures recommend stopping breast-feeding if the agents are to be used. The identification of safe and effective adjuvant therapies to promote help maintain smoking abstinence in post-partum women and are safe to use while breastfeeding could make an important contribution to smoking cessation efforts and cancer prevention.