Skeletal muscle is crucial for maintaining human health and overall quality of life. Acute exercise introduces a multifaceted intracellular stress, with numerous post-translational modifications believed to underpin the health benefits of sustained exercise training. Reactive oxygen species (ROS) are posited to serve as second messengers, triggering cytoprotective adaptations such as the upregulation of enzymatic scavenger systems. However, a significant knowledge gap exists between the generation of oxidants in muscle and the exact mechanisms driving muscle adaptations. This review delves into the current research on subcellular redox biochemistry and its role in the physiological adaptations to exercise. We propose that the subcellular regulation of specific redox modifications is key to ensuring specificity in the intracellular response.