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Available information suggests that currently over 47% of males and 59% of females use dietary supplements for health benefits, and the number of users is rapidly increasing. However, numerous studies published over more than a decade have linked some supplements (including vitamins E, C, D, A, and B, as well as selenium) to no health benefits or even to adverse health effects. Recent studies with negative results, which drew media attention, include the following: a 2008 study on the ability of vitamin E and selenium to lower the risk of prostate cancer was halted amidst fear of potential harm; vitamin C may do more harm than good as it may protect cancer cells; intake of vitamins E and C by 15,000 male physicians for 10 years had no health benefits. In contrast, there are compelling cause and effect data linking the use of folic acid with consistent and significant reductions in fetal adverse pregnancy outcomes, demonstrating no beneficial effects of calcium and vitamin D supplements in improving bone strength and reducing fractures. These equivocal and conflicting findings on the effects of supplements on health outcomes have left consumers confused about their benefits and wary of the possible adverse effects of vitamin and mineral supplementation. The objectives of this session are to characterize the current state of the science as it relates to the impact of vitamin and mineral supplementation on human health, review the statutory and regulatory perspective of vitamin use from a safety perspective, assess the credibility of meta-analysis in the safety assessment of vitamins, and elicit the mechanisms of these interactions—pro-oxidant versus antioxidant effects and beneficial versus adverse effects.