Nuclear factor (NF) κB as a redox sensitive, anti-apoptotic and pro-inflammatory signaling molecule has been studied extensively for more than three decades. Its role in inducing antioxidant enzymes, defending against extracellular and intracellular stress and maintaining redox homeostasis in skeletal muscle has also been recognized. New research continues to explore the polytropic nature of NFκB in cellular function, especially its crosstalk with other important signaling pathways. Understanding of the broad impact of these functions has significant implications in health and disease of skeletal muscle as an organ designed for contraction and mobility. Two important aspects of muscle wellbeing, i.e., disease and aging, are not discussed in this review. This review will provide an update on the new findings related to NFκB involvement in multiple signaling pathways and refresh our knowledge of its activation in skeletal muscle with a special reference to physical exercise.