Due to its interface function between the body and the environment, the skin is chronically exposed to both endogenous and environmental pro-oxidant agents, leading to the harmful generation of reactive oxygen species (ROS). There is compelling evidence that oxidative stress is involved in the damage of cellular constituents, such as DNA, cell membrane lipids or proteins. To protect the skin against the over-load of oxidant species, it contains a well-organised system of both chemical and enzymatic antioxidant which are able to work in a synergistic manner. Skin antioxidant network protects cells against oxidative injury and prevent the production of oxidation products, such as 4-hydroxy-2-nonenal or malonaldehyde, which are able to induce protein damage, apoptosis or release of pro-inflammatory mediators, such as cytokines. When oxidative stress overwhelms the skin antioxidant capacity the subsequent modification of cellular redox apparatus leads to an alteration of cell homeostasis and a generation of degenerative processes. Topical application or oral administration of antioxidants has been recently suggested as preventive therapy for skin photoaging and UV-induced cancer. The recognition that ROS can act as second messengers in the induction of several biological responses, such as the activation of NF-kB or AP-1, the generation of cytokines, the modulation of signalling pathways, etc., has led many researchers to focus on the possible effects of antioxidants in many pathological processes. The recent demonstration that the peroxisome proliferators-activated receptors, whose natural ligands are polyunsaturated fatty acids and theirs oxidation products, have a central role in the induction of some skin diseases, such as psoriasis or acne, has indicated new links between free radicals and skin inflammation. Based on these findings, the review summarises the possible correlations between antioxidant imbalance, lipid oxidative breakage and skin diseases, from both a pathological and therapeutic points of view.