Zinc is an essential catalytic and structural cofactor for many enzymes and other proteins. While Zn2+ is not redox active under physiological conditions, it has been known for many years that zinc deficiency causes increased oxidative stress and, consequently, increased oxidative damage to DNA, proteins, and lipids. These results have indicated that zinc plays an indirect antioxidant role and that dietary inadequacy may contribute to human diseases such as cancer. Recent studies are helping to identify the primary sources of oxidative stress in low zinc. In addition, through studies of the model eukaryotic cell, Saccharomyces cerevisiae, we are now beginning to understand the strategies cells use to limit this stress and reduce its damage.