Cardiovascular disease marks the leading cause of mortality and morbidity in the United States. Pharmacological therapies have been developed to reduce the burden of cardiovascular diseases in the setting of large-scale randomized controlled trials. In contrast, vitamins and minerals have not undergone an equal level of scrutiny, and the evidence of cardiovascular benefit remains elusive. Multivitamins are the most popular over-the-counter supplements in the United States, despite the lack of clear benefit as a means of primary or secondary cardiovascular prevention. Recent studies indicate a potential role of multivitamins in secondary prevention when concomitantly administered with chelation therapy. Additionally, preclinical and observational studies have shown preliminary evidence of cardiovascular protection with dietary supplements such as carnitine, arginine, and coenzyme Q10. This review summarizes the currently available data about the effect of vitamins and other dietary supplements on the cardiovascular system.