Background: The skin is the largest body organ that regulates excretion of metabolic waste products,temperature, and plays an important role in body protection against environmental physical and chemical,as well as biological factors. These include agents that may act as oxidants or catalysts of reactions producingreactive oxygen species (ROS), reactive nitrogen species (RNS), and other oxidants in skin cells. An increasedamount of the oxidants, exceeding the antioxidant defense system capacity is called oxidative stress, leading tochronic inflammation, which, in turn, can cause collagen fragmentation and disorganization of collagen fibersand skin cell functions, and thus contribute to skin diseases including cancer. Moreover, research suggests thatoxidative stress participates in all stages of carcinogenesis. We report here a summary of the present state ofknowledge on the role of oxidative stress in pathogenesis of dermatologic diseases, defensive systems againstROS/RNS, and discuss how physical activity may modulate skin diseases through effects on oxidative stress.The data show duality of physical activity actions: regular moderate activity protects against ROS/RNS damage,and endurance exercise with a lack of training mediates oxidative stress. These findings indicate that the redoxbalance should be considered in the development of new antioxidant strategies linked to the prevention andtherapy of skin diseases.