Within the last decade, many investigators have focused on the physical, neurodevelopmental, and neuropsychological effects of prenatal cocaine exposure on infants and young children. Although inconclusive on many crucial issues, published studies reveal the beginnings of a profile of possible cocaine-related effects on neuropsychological functions subserving arousal and attention regulation. That profile is informed by preclinical studies in which important factors such as duration and type of exposure as well as environmental conditions may be more adequately controlled. In the developing brain, there are a number of candidate mechanisms that account for how prenatal cocaine exposure may interfere with neural ontogeny. This review focuses on the monoamine system, one of the primary sites of action of cocaine in the adult. In the developing organism, monoamines play critical trophic roles through all phases of central nervous system (CNS) ontogeny—cell proliferation, neural migration, growth, maturation, and synaptogenesis. Because of their trophic role in CNS ontogeny, cocaine effects on developing nervous system may be mediated in part through effects on monoamine system ontogeny. In turn, these effects may be expressed behaviorally in disrupted patterns of arousal and attention regulation given that these domains are connected intimately to monoaminergic systems.