Among the non-essential metals, few have rivaled the significance of lead (Pb) within human history in terms of both utility and toxicity. Much of this can be attributed to the use of Pb in plumbing applications, lead-based paints, and leaded gasoline. Today, the primary use for Pb is in the production of batteries and most concern for Pb entering aquatic environments is from point-source discharges related to Pb mining and industrial processing. The bioavailability of Pb to aquatic organisms will depend largely on the pH, alkalinity, hardness, and natural organic matter content of the receiving water. In fish, acute Pb toxicity is due to respiratory asphyxiation under extreme concentrations and the disruption of ionoregulatory homeostasis under more environmentally relevant concentrations. Chronic effects are similar to those in humans, involving primarily hematological and neurological dysfunction. Lead is taken up and elicits its effects by substituting for calcium and potentially other essential divalent cations, such as iron and zinc. Accordingly, Pb is predominantly found within the calcified hard tissues of the skeleton and scales, but also concentrates to a large extent within the blood, gill, and kidney. While great strides have been made in characterizing the uptake, accumulation, and toxicity of Pb in fish, there remains much to be learned regarding the specific transport pathways and internal handling of Pb, as well as the mechanisms of Pb excretion.