Despite clinical experience that spans more than half a century, chelation for toxic heavy metals represents one of the most controversial and misapplied interventions in clinical toxicology. The prompt use of chelating agents to treat acute, life-threatening intoxication is an indication that is largely supported by experimental animal data and limited clinical research. Although chelating agents administered for chronic intoxication may accelerate the excretion of heavy metals, their therapeutic efficacy in terms of decreased morbidity and mortality is largely unestablished. Recent investigations suggest that their use in such settings might be associated with deleterious effects. Careful attention to risk-benefit issues is warranted, particularly in clinical situations in which the etiological role of heavy metals in the patient's illness is in question.