Vitamin C has long been recognized as an important dietary micronutrient based on its ability to prevent scurvy in humans. Moreover, over the past decades, ascorbate has been identified as a powerful redox modulator and named ‘‘the most important antioxidant in plasma''. Several investigators have shown ascorbate to be an excellent biomarker of ‘‘oxidative stress'' in a variety of biological settings from isolated cells to humans. However, in spite of the amazing redox powers of ascorbate, little evidence has been presented until now demonstrating that vitamin C deficiency results in any clinical manifestation beyond that of scurvy. Meanwhile, literally hundreds of millions of people worldwide can be diagnosed with hypovitaminosis C, i.e. a plasma concentration below 23 mmol/L, a condition that is typically chronic due to e.g. sustained malnutrition, smoking or disease. The magnitude of this potential problem has prompted discussions on the possible beneficial effect of supplementation to humans as a preventive measure but so far large clinical trials have shown no clinical relevance of antioxidant supplementation in general. Two possible pathological consequences of marginal vitamin C deficiency are discussed and supported by new in vivo evidence from animal studies. Apparently, vitamin C does matter. . .