Oxidative lesions start accumulating in cells when the oxidant attacks overwhelm the antioxidant defenses. This review will briefly describe red blood cell storage lesions with emphasis on the consequences of oxidation and the cellular defense mechanisms, as well as the methods that can be used to monitor them. The sources of variability in red blood cell storage capacity depend on the donor characteristics, the product processing and the storage conditions. Suggestions to improve the product quality in order to ensure the best efficacy and safety for the transfused patient are also discussed.