Atherosclerotic cardiovascular disease (CVD) is highly prevalent and, despite therapeutic advances, remains a leading cause of morbidity and mortality. Many patients with CVD seek additional alternative therapies when symptoms are not controlled with evidence-based therapies. Although its therapeutic efficacy is unproven, chelation therapy with ethylenediamine tetra acetic acid (EDTA) is increasingly being used in patients with CVD. Early studies of chelation in atherosclerotic CVD provided the basis for the randomized Trial to Assess Chelation Therapy (TACT), in which chelation with disodium EDTA was compared with placebo in patients who had experienced a myocardial infarction. Here, we discuss the results, limitations, and implications of TACT in the context of other studies in the field. We believe that the findings from TACT are not robust and do not marshal evidence in support of the potential clinical use of chelation therapy for CVD, with the potential exception of certain high-risk cohorts such as patients with diabetes mellitus. Therefore, chelation is unlikely to become a widely-accepted approach until additional data are available.