Chelation therapy has been used to treat heavy metal poisoning since World War II. The term chelate was coined by the analytical chemist, G.T. Morgan in 1920. Chelate is the Greek word for claw. Alfred Werner, the son of a factory foreman and the Father of Coordination Chemistry, was awarded the 1913 Nobel Prize for developing this concept of chelation therapy. In chelation therapy, the ring within the molecule of the chelator captures and firmly binds the metallic ions. Thus chelation therapy treats heavy metal poisoning by forming complexes with the molecules of the heavy metal, which are then excreted in urine. Up to a certain stage, the subsequent fall in the metal stores can help reverse the toxicity.

Dimercaprol, more commonly known as BAL was the first agent used in chelating therapy. During the II World War, biochemists at Oxford University developed BAL as an antidote for the war gas Lewisite. Exposure to Lewisite causes acute arsenical blisters and systemic arsenic poisoning. That is how the first chelating agent, Dimercaprol, came to be known as British Anti-Lewisite (BAL). Soon the effectiveness of Dimercaprol in the chelation therapy of heavy metal poisoning became evident. Peters noted that BAL ointment had proved very successful in cases of industrial arsenical accidents. Injectable forms of BAL were also found to be effective in chelation therapy. By 1947, 32 articles were published or in press on the therapeutic value of BAL. BAL became the chelation therapy of choice in arsenic, antimony, gold, and mercury poisoning.

A study conducted by Denny-Brown and Porter in 1951 found other uses of BAL as a chelating agent. BAL was noted to be an effective in chelation therapy of Wilsons disease wherein excessive amount of Copper accumulates in the body. BAL chelates copper and removes it from body by excretion. At this time a need for better chelators was felt. BAL was found to be associated with various toxic effects and moreover, chelation therapy with BAL became ineffective in most patients after some time.

In 1956, Walsh first advocated use of Penicillamine, another chelating agent in treatment of Wilsons disease. Penicillamine was found to be more effective and less toxic. It is now commonly used in treatment of Wilsons disease.

In the 1950s and 1960s, there was an explosion of publications on the effects of various chelating agents in animals and human beings. Ferdinand Munz had discovered EDTA (ethylenediamine tetraacetic acid), a synthetic amino acid with chelating properties way back in 1938. By 1951, EDTA was widely used in treatment of inorganic lead poisoning and is approved by FDA for the same.

The numerous adverse effects of BAL, and the need to give it intravenously, stimulated further research in this field. It was on the whole found to be inefficient in the chelation therapy of chronic mercury poisoning. Water soluble derivatives of BAL, like Meso-2, 3-dimercaptosuccinic acid (DMSA) and 2, 3-dimercaptopropane-1-sulfonic acid (DMPS) were developed. They were found to be highly effective in treatment of mercury and lead poisoning.

DMSA and DMPS exhibit very low toxicity and are valuable oral chelating agents. In 1999, Baun opined that, unlike BAL, DMSA can be used in treatment of organic mercury poisoning. Patients with chronic mercury poisoning can now receive oral chelation therapy with DMSA, eliminating the need for a hospital admission. In 2003, Bose-OReilily and other found that oral DMSA was highly effective in treating chronic mercury toxicity among the inhabitants of gold-mining area in Philippines. DMSA was licensed by FDA for treatment of lead poisoning in 1991. Given their proven advantages over BAL, DMSA and DMPS have gained increased acceptance among clinicians. They have improved the management of heavy metal poisoning.

BAL derivatives are not effective in chelating iron. Previously, deferoxamine was the only iron-chelator available which needed to be given as long intravenous infusions. Recently, deferasirox, an oral iron-chelator was developed. Deferasirox is approved for oral chelation therapy for disorders like sickle cell anemia, which are characterized by excess accumulation of iron in body.