Contraction-induced production of reactive oxygen species (ROS) has been implicated in oxidative stress to skeletal muscle for the past few decades. As research advances more evidence has revealed a more complete role of ROS under both physiological and pathological conditions. The current review postulated that moderate intensity of physical exercise has antioxidant and anti-inflammatory effects due to the operation and cross-talks of several redox-sensitive signal transduction pathways. The functional roles and mechanisms of action of the nuclear factor κB, mitogen-activated protein kinase, and peroxisome proliferator-activated receptor γ co-activator 1α are highlighted.