Muscle atrophy and weakness, characterized by loss of lean muscle mass and function, has a significant effect on the independence and quality of life of older people. The cellular mechanisms that drive the age-related decline in neuromuscular integrity and function are multifactorial. Quiescent and contracting skeletal muscle can endogenously generate reactive oxygen and nitrogen species (RONS) from various cellular sites. Excessive RONS can potentially cause oxidative damage and disruption of cellular signaling pathways contributing to the initiation and progression of age-related muscle atrophy. Altered redox homeostasis and modulation of intracellular signal transduction processes have been proposed as an underlying mechanism of sarcopenia. This chapter summarizes the current evidence that has associated disrupted redox homeostasis and muscle atrophy as a result of skeletal muscle inactivity and aging.