Chelation therapy, typically used to remove heavy metal toxins, has also been controversially used as a treatment for coronary artery disease. The first Trial to Assess Chelation Therapy (TACT) aimed to provide evidence on chelation therapy’s potential for benefit or harm. Although TACT had some significant results, the trial does not provide enough evidence to recommend routine chelation therapy and has limitations. The second TACT was recently funded reigniting a discussion about the value of chelation therapy, its efficacy, and allocation of research resources. Despite limited evidence, patients continue to pursue chelation therapy as a treatment for coronary artery disease. As the medical community has a responsibility to understand all treatments patients pursue, it is important to comprehensively appraise chelation therapy for cardiovascular disease. Understanding the background of heavy metal toxicity, the putative target of chelation therapy, on the cardiovascular system is important to contextualize the role of chelation therapy in cardiovascular disease prevention. We review the clinical evidence of heavy metal toxicity and cardiovascular disease, and available clinical trial data on use of chelation therapy to minimize the cardiovascular burden of heavy metal toxicity.