Generation of reactive oxygen species (ROS) is a ubiquitous biological phenomenon in eukaryotic cell life. During the past two decades, much attention has been paid to the detrimental effects of ROS such as oxidative stress, pathogenesis and aging. However, there is now increasing evidence and recognition that ROS are not merely damaging agents inflicting random destruction to the cell structure and function, but useful signaling molecules to regulate growth, differentiation, proliferation, and apoptosis, at least within the physiological concentration. In skeletal muscle contractile activity has been shown to upregulate antioxidant defense systems and ROS has been postulated to be essential in this adaptation. Available research data suggest that nuclear factor (NF)kappaB and mitogen-activated protein kinase (MAPK) play a critical role in the relay of oxidative stress signals to gene expression apparatus in the myocytes under a variety of physiological and pathological conditions. This mini-review will discuss the main mechanisms and gene targets for these antioxidant signaling pathways during exercise, inflammation and aging.