Our interest in the role of reactive oxygen species (ROS) in skeletal muscle was ignited in the early 1980’s by an upsurge in publicity about nutritional myopathies that were economically important in some farm animals, such as the so-called “White Muscle Disease” in cows and sheep. These disorders had been recognised to be caused by selenium or vitamin E deficiency. This prompted studies to determine common mechanisms that might underlie these disorders and potentially be relevant to human myopathies involving David Jones, Richard Edwards and myself in the muscle group based at University College, London [1, 2]. An understanding of the roles of these nutrients as antioxidants and the recognition that skeletal muscle generates free radicals and other ROS during contractile activity has stimulated research into potential physiological and pathophysiological roles of ROS in skeletal muscle. Superoxide is generated by NADPH oxidases during muscle contractile activity. It is rapidly converted to hydrogen peroxide (H2O2) which acts as a signalling molecule to stimulate multiple adaptations to contractile activity through redox-regulated signalling pathways. These physiological pathways appear to be modified by ageing leading to attenuation of some specific responses to muscle contractile activity and exercise in older humans and animals [3]. Our studies have recently focussed on understanding how this attenuation of redox responses occurs in ageing and indicate that mitochondria plays a major role. In older humans and mice, muscle shows substantial evidence of motor unit remodelling and focal denervation which has been shown to be associated with a substantial increase in mitochondrial peroxide generation by denervated and neighbouring innervated muscle fibres [4], leading to a local disruption of redox signalling. How such changes contribute to the loss of skeletal muscle mass and function that accompanies ageing remains a subject of extensive study.