Since the first clear observation that skeletal muscle contained increased amounts of free radical species in the early 1980s, there has been increasing interest in how such species are formed and what functions they might have in skeletal muscle. Superoxide and nitric oxide are formed in increased amounts in skeletal muscle during contractile activity and these species together with the important derivative, hydrogen peroxide, are now recognised to play an important role in the physiological responses of muscle to contractile activity or exercise. In this chapter the potential sites for generation of superoxide and hydrogen peroxide during contractile activity will be examined together with the mechanisms for their formation. A major role for these species appears to be to signal the initiation of responses by which the muscle adapts to contractile activity and the potential mechanisms by which they exert such effects will be discussed. This appears to be a still poorly understood area of skeletal muscle biology which however has the potential for exploitation to optimise the beneficial effects of exercise and may well point to pharmacological approaches that can provide the benefits of exercise in immobile, ill or infirm subjects that are unable to take part in traditional exercise regimens.