Increments of oxidative stress have been addressed as one potential cause for the accelerated atherosclerosis of chronic kidney disease patients. Ascorbate represents one of the most prominent antioxidants both in plasma as well as intracellulary, exerting beneficial effects by an inhibition of lipid peroxidation and by reducing endothelial dysfunction. However, in the presence of transition metals like iron, ascorbate may give rise to an increased generation of oxidants, and ascorbylation may impose additional carbonyl stress to uremic patients. Unsupplemented dialysis patients have reportedly lower plasma levels of ascorbate in comparison to healthy controls, mostly due to a loss into the dialysate or, in case of not dialyzed patients, increased urinary losses. Currently, 60 mg of ascorbate are recommended for chronic kidney disease patients, and 1–1.5 g of oral ascorbate/week in case of suspected subclinical ascorbate deficiency or 300 mg parenteral ascorbate/dialysis session, respectively. Ascorbate’s role in modifying arterial blood pressure remains unclear, but anemic patients with functional iron deficiency might benefit from short-term, moderately dosed ascorbate supplements.