The first suggestion that physical exercise results in free radical-mediated damage appeared in 1978, and since that time the sources of oxidant production during exercise continue to be debated. Many researchers focused on the damaging effects of oxidants in muscle (oxidative damage of proteins and lipids), but the examination of cell-signaling effects of free radicals on muscle activity became today's main issue. Free radicals can modulate a number of cell signaling pathways and regulate the expression of multiple genes, contributing to the muscle adaptation on exercise and improving the muscle force production. Those effects are provided by changes in calcium handling by muscle cells or changing in the sensitivity of myofilaments to calcium. As a conclusion we can say that low and physiological levels of free radicals are required for normal force production in skeletal muscle and antioxidant adaptation, while high levels of free radicals promote contractile dysfunction resulting in muscle weakness and fatigue.