Optimal use of chelation in metal intoxication is an important clinical challenge. During the last two decades, important developments have occurred in the possibility and clinical practice of chelation treatment of acute and chronic metal poisonings. Thus, DMSA and DMPS have gained more general acceptance among clinicians, undoubtedly improving the management of human metal intoxications. Recent case reports on clinical treatment of acute metal intoxications indicate, however, that the older, more toxic and less efficacious chelators, especially BAL, are still used in surprisingly many cases. This is odd, as DMPS and DMSA are available as cheaper, more stable preparations for oral or parenteral use, as compared to the expensive, unstable preparations of BAL suited for im use only. The development in experimental animals of chelating agents efficiently mobilizing aged intracellular cadmium deposits offers the possible future development of less toxic compounds, that may be used also with lead and mercury. The development of a safe DMPS mobilization test for inorganic mercury may hopefully lead to development of further diagnostic tools, that can be used more safely than the traditional EDTA test for lead exposure. Despite the improvement of chelation treatment of several chronic metal intoxications in experimental animals, development of new, safe chelators for long-term clinical chelation of lead, organomercury and cadmium deposits is an important challenge for the future.