Health status is determined by the balance of oxidants and antioxidants which protects healthy cells against the threat of internal and external risk factors. Antioxidants such as ascorbate (vitamin C, ascorbic acid) are of fundamental importance in this respect. Ascorbate neutralizes potential damage caused by cellular oxidative stress which may be the greatest risk of damage to healthy tissue. Cellular oxidative stress is mediated by external factors (e.g. psychological stress, physical exertion, drugs, various diseases, environmental pollution, preservatives, smoking, and alcohol) and internal factors (products of cellular metabolism including reactive oxygen species). When the products of oxidative stress are not sufficiently neutralized, healthy cells are at risk for both mitochondrial and DNA damage. In the short term, cell function may deteriorate, while an increased production of proinflammatory cytokines over time may lead to the development of chronic inflammatory changes and diseases, including cancer. Although pharmaceutical research continues to bring effective chemotherapeutic agents to the market, a limiting factor is often the normal tissue and organ toxicity of these substances, which leads to oxidative stress on healthy tissue. There is increasing interest and imperative to protect healthy tissues from the negative effects of radio-chemotherapeutic treatment. The action of ascorbate against the development of oxidative stress may justify its use not only in the prevention of carcinogenesis, but as a part of supportive or complementary therapy during treatment. Ascorbate (particularly when administered parentally at high doses) may have antioxidant effects that work to protect healthy cells and improve patient tolerability to some toxic radio-chemotherapy regimens. Additionally, ascorbate has demonstrated an immunomodulatory effect by supporting mechanisms essential to anti-tumor immunity. Intravenous administration of gram doses of vitamin C produce high plasma levels immediately, but the levels drop rapidly. Following oral vitamin C administration, plasma levels increase slowly to relatively low values, and then gradually decay. With an oral liposomal formulation, significantly higher levels are attainable than with standard oral formulations. Therefore, oral administration of liposomal vitamin C appears to be an optimal adjunct to intravenous administration. In this review, the basic mechanisms and clinical benefits of ascorbate as an antioxidant that may be useful as complementary therapy to chemotherapeutic regimens will be discussed.