The central nervous system appears to be the primary target organ for lead. Children in particular remain at risk for the central nervous system effects of lead, not only in many American cities but also in numerous developing countries where the use of leaded gasoline continues. Those same children, moreover, may sustain many of the risk factors, such as low socioeconomic status and calcium and iron insufficiencies, known to exacerbate the manifestations of lead exposure, including its central nervous system effects. Physiologic conditions associated with bone resorption, including pregnancy, lactation, and aging can also potentiate the central nervous system effects of lead and enhance exposure of adults. Questions regarding safe and efficacious diagnosis and treatment of elevated lead burden, particularly as they relate to central nervous system-based effects of lead have recently been raised. Clearly, greater education of and awareness in the medical community are needed for recognition of problems accruing from lead exposure.