Increasing evidence supports the role of metals/metalloids including arsenic, cadmium, and lead as cardiovascular risk factors. Exposure to cadmium and lead increased rapidly in most countries following the 1940s. Their half-lives, moreover, are extremely long, as they accumulate in bone tissue for lead and in soft tissues for cadmium. Aging populations today have thus accumulated more lead and cadmium in the body than at any other time in history. Arsenic is found mostly in groundwater and food, in particular rice affecting general populations worldwide. Several systematic reviews have evaluated studies investigating the association between lead and cadmium with incident cardiovascular disease (coronary heart disease and stroke). Bone and blood lead, urine and blood cadmium, and water and urine arsenic are consistently associated with increased cardiovascular mortality and/or incidence in multiple studies after adjustment for traditional risk factors. Observational studies are limited by confounding and selection bias. We also considered evidence from a double blind randomized clinical trial (Trial to Assess Chelation Therapy (TACT)) comparing the effects of edetate disodium, a chelating agent that excretes both lead and cadmium, to placebo in post-myocardial infarction participants (N=1708). The primary endpoint was a composite of all-cause mortality, myocardial infarction, stroke, coronary revascularization, and angina hospitalization. Participants receiving edetate disodium-based infusions showed a reduction in the primary composite endpoint by 18% (hazard ratio 0.82; 95% CI, 0.69-0.99, p = 0.035; number needed to treat (NNT) to prevent 1 event over 5 years of follow-up was18). TACT2, an ongoing NIH trial is replication trial and will also evaluate the possibility that lead and cadmium mediate the cardiovascular benefit of edetate disodium in post-myocardial infarction patients. The well-established effect of metals on oxidative stress is a possible mechanisms for metal-related cardiovascular disease. In conclusion, metals and metalloids are possible cardiovascular risk factors. Public health and clinical interventions are urgently needed for the prevention and control of metal-related cardiovascular disease in general populations around the world.