The chemical solution most often used in chelation therapy, EDTA, was first made in Germany in the 1930s. It is now widely accepted as an effective treatment for heavy metal poisoning.

In the 1950s, some scientists theorized that EDTA could remove calcium from the body. Calcium can build up on artery walls, eventually causing heart disease, and it was theorized that use of EDTA could unclog blocked arteries. In some early studies, researchers reported positive results among patients with heart disease who received EDTA. Some said that chelation therapy relieved chest pain caused by blocked arteries. These first observations have not been confirmed by larger, more rigorous studies, but they led some practitioners to begin using chelation therapy for heart and circulatory problems and, later, for several other illnesses. It is estimated that tens of thousands of Americans currently undergo chelation therapy for heart disease.

DMSO was first discovered in the mid- to late nineteenth century and has been used as an industrial solvent for more than a hundred years. In the 1950s, it was discovered that DMSO could protect cells from the damage of freezing. In the 1960s, Dr. Stanley Jacob, one of the main proponents of DMSO, began to study other medicinal properties of the substance. In 1965, clinical trials of DMSO were stopped due to questions about its safety. However, in the 1970s, DMSO was approved a prescription drug for a type of bladder inflammation in humans.