Mitochondrial biogenesis is critical for the normal function of cells. It is well known that mitochondria are produced and eventually after normal functioning they are degraded. Thus, the actual level of mitochondria in cells is dependent both on the synthesis and the degradation. Ever since the proposal of the mitochondrial theory of ageing by Jaime Miquel in the 70's, it was appreciated that mitochondria, which are both a target and a source of radicals in cells, are most important organelles to understand ageing. Thus, a common feature between cell physiology of ageing and exercise is that in both situations mitochondria are critical for normal cell functioning. Mitochondrial synthesis is stimulated by the PGC-1α–NRF1–TFAM pathway. PGC-1α is the first stimulator of mitochondrial biogenesis. NRF1 is an intermediate transcription factor which stimulates the synthesis of TFAM which is a final effector activating the duplication of mitochondrial DNA molecules. This pathway is impaired in ageing. On the contrary, exercise, particularly aerobic exercise, activates mitochondriogenesis in the young animal but its effects on mitochondrial biogenesis in the old animal are doubtful. In this chapter we consider the interrelationship between mitochondrial biogenesis stimulated by exercise and the possible impairment of this pathway in ageing leading to mitochondrial deficiency and eventually muscle sarcopenia.