Iron depletion is a known risk for adult blood donors, but recent studies indicate the prevalence of iron depletion is higher in teenage blood donors. Teenage donors account for more than 10% of the blood collected in the United States and are important for maintaining component availability. Evidence of harm from iron depletion has not been demonstrated, but the area would benefit from further scientific inquiry. Options to protect against iron depletion exist, but each has limitations including cost, logistics, and potential negative impact on blood supply. Blood centers should communicate with donors and make efforts to mitigate these risks.