Skeletal muscle fiber has a great ability to hypertrophy during growth and in response to exercise stimuli, and atrophy during aging and in response to disuse. Because the muscle fiber is a multinucleated cell, the region of cytoplasm governed by a single myonucleus (myonuclear domain; MND) is a very important factor for understanding muscle plasticity. Although the MND size varies with fiber type, metabolic property and species, it was considered that the size was maintained constantly during muscle adaptation. Recently, however, there have been many studies demonstrating the variability of the MND size. In some of these studies, it is hypothesized that muscle hypertrophy is achieved by increase in protein synthesis rate until the ‘ceiling’ of MND size and subsequent addition of myonuclei by satellite cell activation. On the other hand, during muscle atrophy, the myonuclei seems to be long lasting as ‘muscle memory’ storing information about previous size to prepare for recovery of muscle fiber. Understanding the variability of MND size more deeply would provide fundamental insights into the mechanism of skeletal muscle plasticity.