Tobacco use in pregnancy is a leading cause of perinatal morbidity and contributes in major ways to attention deficit hyperactivity disorder, conduct disorders and learning disabilities that emerge in childhood and adolescence. Over the past two decades, animal models of prenatal nicotine exposure have demonstrated that nicotine is a neurobehavioral teratogen that disrupts brain development by preempting the natural, neurotrophic roles of acetylcholine. Through its actions on nicotinic cholinergic receptors, nicotine elicits abnormalities of neural cell proliferation and differentiation, promotes apoptosis and produces deficits in the number of neural cells and in synaptic function. The effects eventually compromise multiple neurotransmitter systems because of the widespread regulatory role of cholinergic neurotransmission. Importantly, the long-term alterations include effects on reward systems that reinforce the subsequent susceptibility to nicotine addiction in later life. These considerations strongly question the appropriateness of nicotine replacement therapy (NRT) for smoking cessation in pregnant women, especially as the pharmacokinetics of the transdermal patch may actually enhance fetal nicotine exposure. Further, because brain maturation continues into adolescence, the period when smoking typically commences, adolescence is also a vulnerable period in which nicotine can change the trajectory of neurodevelopment. There are also serious questions as to whether NRT is actually effective as an aid to smoking cessation in pregnant women and adolescents. This review considers the ramifications of the basic science findings of nicotine's effects on brain development for NRT in these populations.