Skeletal muscle has been recognized as a potential source for generation of reactive oxygen and nitrogen species for more than 20 years. Initial investigations concentrated on the potential role of mitochondria as a major source for generation of superoxide as a "by-product" of normal oxidative metabolism, but recent studies have identified multiple subcellular sites, where superoxide or nitric oxide are generated in regulated and controlled systems in response to cellular stimuli. Full evaluation of the factors regulating these processes and the functions of the reactive oxygen species generated are important in understanding the redox biology of skeletal muscle.