Oxidative stress is induced by a wide range of environmental factors including UV stress, pathogen invasion and oxygen deprivation/hypoxia. Generation of reactive oxygen species (ROS) is a characteristic feature of such stress conditions. Intracellular oxidation, mediated by ROS is prevented by an antioxidant system that includes low molecular mass antioxidants such as vitamin C, glutathione, tocopherols and ROS-interacting enzymes such as superoxide dismutase (SOD), peroxidases and catalases. Antioxidants act in a cooperative network, employing a series of redox reactions. Interactions between vitamin C and glutathione and and phenolic compounds are well known. Apart from stress conditions, ROS is generated during cytokine and growth factor-induced signal transduction pathways. The redox-regulated transcription factors in turn activate transcription from oxidant-responsive genes, but under extreme physiological conditions these show aberrant functions resulting in the onset of oncogenesis. Oxidant stress mediates acute barrier dysfunctional responses and vascular disorders through several pathways. ROS may activate phospholipases such as PLC, PLD and PLA2 which further generate a multitude of cellular messengers and cofactors.Under such stress conditions, vitamin C acts as a primary antioxidant in plasma and within cells it quenches ROS. Under physiological conditions, vitamin C predominantly exists in its reduced form, ascorbic acid or ascorbate. It also exists in trace quantities in the oxidized form dehydroascorbic acid. At physiological pH, ascorbate occurs in the monoanion form. Loss of the first electron results in the formation of ascorbate free radical (AFR). AFR is not very reactive and mild oxidants can remove a second electron and convert the AFR to dehydroascorbic acid. There are two mechanisms for transporting vitamin C into cells. GLUT transporters carry dehydroascorbic acid into the cell. Once inside the cell, dehydroascorbic acid is rapidly reduced and accumulates as vitamin C. Dehydroascorbic acid can be reduced back to vitamin C by enzymes such as thioredoxin reductase and dehydroascorbic acid reductase. The second transport system involves the direct transport of vitamin C via sodium-dependent ascorbate co-transporters (SVCT). Increased intracellular levels of vitamin C and dehydroascorbic acid inhibit ROS-mediated signaling events. For example, dehydroascorbic acid inhibits IKK which is activated by ROS, thus inhibiting NF-κB mediated signal transduction. These actions point to vitamin C as a potent antioxidant and a regulator of redox-signal transduction in host defense cells.