Lead (Pb) has been recognized as a human toxin for thousands of years. In biological systems, sulfur-, oxygen- and nitrogen-containing groups coordinate lead in a variety of geometries. Upon ingestion by humans, lead is absorbed through the stomach, released into the blood and coordinated by glutathione and a variety of zinc and calcium proteins including δ-aminolevulinic acid dehydratase (ALAD), zinc finger transcription factors and calmodulin. Metal substitution and indiscriminate binding to proteins causes a loss of function, reflected in the diverse symptoms of lead poisoning. Although some lead binding proteins are induced in the presence of lead, their role in detoxification in humans is unclear. However, several types of bacteria have evolved defence mechanisms for the uptake, storage and exportation of lead. The proteins involved in regulating these defences, such as PbrR, are extremely selective for lead.