•Lead is a neurotoxin with a long history of use by humans.•Effects of low-level lead exposure on behavior and cognition are summarized.•Mechanisms of action for lead include neuronal and non-neuronal CNS targets.•The present level of concern set by the CDC for lead in blood is 5 μg/dL.•Lead levels below 3 μg/dL produce maladaptive behavior and cognitive deficits. Lead is a neurotoxin that produces long-term, perhaps irreversible, effects on health and well-being. This article summarizes clinical and preclinical studies that have employed a variety of research techniques to examine the neurotoxic effects of low levels of lead exposure. A historical perspective is presented, followed by an overview of studies that examined behavioral and cognitive outcomes. In addition, a short summary of potential mechanisms of action is provided with a focus on calcium-dependent processes. The current level of concern, or reference level, set by the CDC is 5 μg/dL of lead in blood and a revision to 3.5 μg/dL has been suggested. However, levels of lead below 3 μg/dL have been shown to produce diminished cognitive function and maladaptive behavior in humans and animal models. Because much of the research has focused on higher concentrations of lead, work on low concentrations is needed to better understand the neurobehavioral effects and mechanisms of action of this neurotoxic metal.