The muscle cell is multinuclear and each nucleus controls transcriptional activity in the surrounding territory of cytoplasm called myonuclear domain (MND). MND size varies with the fiber type and is inversely proportional to the muscle fiber oxidative capacity. Change in MND size precedes change in myonuclei count during post-natal growth and most conditions of muscle fiber hypertrophy, suggesting that the myonuclei have the ability to enhance their synthetic capacity according to cell size, functional and metabolic needs. MND size has a “ceiling” limit during hypertrophic process beyond which extra myonuclei are donated by satellite cell to support further muscle growth. During ageing-related atrophy, myonuclei are not lost but an unequal distribution is reported. Ageing myonucleus still responds to resistant exercise and hormone replacement therapy (HRT) by enhancing its transcriptional capacity. Thus the MND size is far from constant and modulates itself to contribute to the muscle remodeling in various conditions.