The epidermal antioxidant network consists of a complex defense system against oxidative stress in which the function of one antioxidant often supplements or regenerates another antioxidant. These important antioxidants consist of detoxication enzymes and small molecule antioxidants, which can be further characterized as water-soluble and lipid-soluble antioxidants. In the case of the enzymes, each one contains a cofactor, which carries out the antioxidant activity—usually by electron transfer reactions that neutralize reactive oxygen species (ROS). The behavior of small molecule antioxidants is partially determined by the solubility—either lipid- or water-soluble. Lipid-soluble antioxidants are found in cell membranes and other lipid-rich regions, for example, embedded in the lipid lamellar structures of the stratum corneum. One would expect to find most water-soluble small antioxidants in the cytosol; however, keep in mind that many free radical reactions also take place at interfaces. In general, small molecule antioxidants can act as preventive antioxidants or radical scavenging antioxidants. Preventive antioxidants keep radicals from forming in the first place, while radical scavenging antioxidants prevent the initiation of free radical chain reactions or they stop free radical chain reactions from propagating. Nevertheless, when antioxidants are not able to prevent free radical damage, the organism, or in this case the skin, is found in a state of oxidative stress leading to disease, cancer, or aging.