Exercise imposes cellular stress on contracting skeletal muscle fibers, forcing them to complete molecular adaptations to maintain homeostasis. There is mounting evidence that redox signaling by reactive oxygen species (ROS) is vital for skeletal muscle exercise adaptations across many different exercise modalities. The study of redox signaling is moving towards a growing appreciation that these ROS do not signal in a global unspecific way, but rather elicit their effects in distinct subcellular compartments. This short review will first outline the sources of ROS in exercising skeletal muscle and then discuss some examples of exercise adaptations, which are evidenced to be regulated by compartmentalized redox signaling. We speculate that knowledge of these redox pathways might one day allow targeted manipulation to increase redox-signaling in specific compartments to augment the exercise-hormetic response in health and disease.