Regular exercise can increase the endurance capacity and improve cardiovascular health. In addition, regular exercise has also been reported to benefit the metabolic adaption and physiological structure, especially in the skeletal muscle. The phenotype of skeletal muscle is associated with human performance and health, and skeletal muscle oxidative capacity is thought to be a key determinant of exercise tolerance in humans. More recently, the protein deacetylase sirtuin 1 (SIRT1), is proposed to be a critical regulator of exercise-induced muscle transcription and remodeling, primarily mediated via its ability to deacetylate and activate peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α). The SIRT1/PGC-1α pathway drives the fiber-type switching in skeletal muscle and increases the aerobic capacity. Therefore, the SIRT1/PGC-1alpha activity will directly regulate the downstream genes expression, as well as mitochondrial dysfunction of skeletal muscle involved in tissue responses to injury. The present review systematically investigates the role of SIRT1/PGC-1a signaling pathway in exercisestimulated mitochondrial biogenesis of skeletal muscle tissues. Our review article also provides detail information on recent molecular insights into the benefits of exercise.