Children in the United States are exhibiting extremely high levels of attentional and learning disabilities. Although lead has been eliminated from many industrial products, children continue to come into contact with it, such as in toys and cosmetics. Lead exposure occurs most commonly in poor, urban populations, and can exacerbate psychiatric disorders associated with stress. We present 1) an overview of lead exposure; 2) a detailed summary of current research on the molecular synergy of toxicity caused by lead and stress; 3) a review of human studies that appear to correlate with these molecular findings, including understanding nutrition, environmental enrichment, and caregiving as risk modifiers; and 4) a systematic approach for mental health practitioners in managing children presenting with multiple symptoms and risk factors for mental health conditions. In this article, we review some of the clinical and scientific challenges that relate to the assessment and treatment of children presenting for mental health care who may have potential lead exposure.