Conclusions: Due to the debilitating nature of cancer- and chemotherapy-related fatigue and other side-effects that impact on QOL, any therapy that can alleviate these symptoms will significantly improve the QOL of sufferers. A number of phase I clinical trials have shown that high-dose IV vitamin is safe and well tolerated in cancer patients, either as a monotherapy (8, 45) or in combination with other chemotherapeutic agents (28, 46). Although direct anti-cancer effects of IV vitamin C have not yet been confirmed by these small studies, there is consistent evidence that IV vitamin C can improve cancer patient’s QOL (6–9) and decrease multiple aspects of fatigue (22, 23). Patients with cancer-related fatigue are often prescribed central nervous system stimulants, despite a limited evidence base, and the fact that these are often ineffective (50). Thus, if future intervention studies indicate that IV vitamin C is an effective anti-fatigue therapy, this will reduce the use of ineffective medications and their accompanying side-effects. Overall, additional well-designed placebo-controlled studies investigating the effects of IV vitamin C on QOL of cancer patients appear warranted.