Numerous epidemiological studies in the human population clearly indicate that smoking while pregnant has deleterious effects on fetal development as well as long-term adverse consequences on postnatal development and maturation of several organ systems. Low birth weight, sudden infant death syndrome (SIDS), behavioral disorders including attention deficit hyperactivity disorder (ADHD), externalizing and internalizing behavioral problems and conduct disorders in children have all been linked to prenatal exposure to tobacco smoke. The major pharmacologically active chemical found in tobacco smoke is nicotine, and prenatal exposure to nicotine has been shown to have significant effect on the development of multiple organ systems, including the nervous, respiratory, and cardiovascular systems. In this review, we define mainstream and sidestream smoke, summarize the major classes of compounds found in cigarette smoke, and describe how use of laboratory animal models can be used to assess mechanisms of toxicity and risk in the human population in general. We then discuss the association with smoking during pregnancy and the occurrence of reduced lung function, low birth weight, the incidence of congenital structural malformations, SIDS, ADHD, cognitive impairment, and mood disorders in children, and review pertinent experimental studies using a variety of animal models of developmental nicotine exposure, including, rats, mice, monkeys, lambs, and pigs that have increased our understanding of the pathophysiology of these disorders.