Thirty years ago, an epidemic of crack cocaine abuse swept the country and had particularly devastating effects on poor individuals and minorities. This heavily addictive form of smoked cocaine ensnared many young women who became pregnant. At the time, several clinical reports from small cohorts of cocaine-exposed infants suggested severe adverse neurobehavioral outcomes, leading to the designation “crack babies.” Nevertheless, thoughtful clinicians raised concerns about facile inferences that cocaine alone caused this phenotype.1,2 They noted a number of other well-established risk factors for these adverse outcomes that could be difficult to disentangle from exposure to cocaine including concurrent use of tobacco and alcohol, known behavioral teratogens, poor perinatal care, and other adverse consequences of poverty such as poor diet. Cocaine causes its rewarding effects by inhibition of the dopamine transporter, which activates reward circuits in the forebrain.3 However, it is also an inhibitor of the norepinephrine transporter as well as the serotonin transporter, thereby potentiating the effects of these other 2 neurotransmitters. These “biogenic amine” neurotransmitter systems, the cell bodies of which are located in the midbrain-brainstem and compose the reticular core, are among the earliest neural systems to develop in the brain.4 Preclinical research has demonstrated that during fetal brain development they play important roles in modulating neurogenesis, neuronal migration, neuronal differentiation, and synaptogenesis.5 Thus, it is not surprising that studies in fetal rodents have demonstrated that cocaine causes a persistent disruption in dopamine signaling, cortical GABAergic function, and pyramidal neuron dendritic structure in the prefrontal cortex, a dopamine-rich region.6 Other studies have shown that inhibition of serotonin transport in the fetal brain disrupts the formation of the so-called barrel fields in the rodent primary sensory cortex, a cortical structure that mediates sensory processing.7 In addition to these developmental teratogenic effects, cocaine is a vasoconstrictor that can impair placental perfusion as well as fetal brain circulation, directly compromising fetal integrity.8 Finally, Lester and Padbury9 have proposed a third pathophysiologic mechanism for the adverse effects of fetal cocaine exposure: it acts as a profound stressor that alters fetal programming and gene expression that results in persistent dysregulation of catecholamine and neuroendocrine function. In the April issue of JAMA Pediatrics, Liu et al reported the effects of fetal exposure to cocaine or tobacco on adolescent brain morphology as determined by magnetic resonance imaging. Fetal exposure to either cocaine or tobacco has previously been reported to adversely affect brain development. Thus, this study attempted to define the alterations that are specifically associated with each substance. They found thinning of the right dorsal lateral prefrontal cortex in adolescents with fetal cocaine exposure and a decrease in the volume of the globus pallidum in children with fetal tobacco exposure. Interestingly, enlarged thalamus in either fetal cocaine or fetal tobacco exposure correlated with the increased impulsivity. The results in this study along with recent functional brain imaging findings10 in adolescents with a history of fetal cocaine exposure dovetail with the rodent research indicating that cocaine exposure in utero disrupts normal brain development, resulting in persistent structural and functional changes that have clear behavioral manifestations. So, cocaine, along with ethanol and nicotine, is an unequivocal neurobehavioral teratogen and a preventable cause of psychopathology in youth.