Muscle memory has been used to describe the observation that various muscle-related tasks seem to be easier to perform after previous practice, even if the task has not been performed for a while. It is as if the muscles “remember”. The term could relate to tasks as disparate as playing the clarinet and weight-lifting, i.e., the observation that strength trained athletes experience a rapid return of muscle mass and strength even after long periods of inactivity. Until recently such effects were attributed solely to motor learning occurring in the central nervous system. Long-term effects of previous training on the muscle fibers themselves, however, have recently also been observed related to strength training. Until recently it was generally assumed that the effects of exercise on muscle was reversible, and that after a long period of de-training the muscle fibers returned to their previous state. For strength training this view was recently challenged by using in vivo imaging techniques revealing specific long lasting structural changes in muscle fibers after a strength-training episode. The notion of a memory mechanism residing in the muscle fibers might have implications for health related exercise advice, and for exclusion times after doping offences. Muscle memory is probably related to the cell nuclei residing inside the muscle fibers, as is described below. The muscle cells are the largest cells in the body with a volume thousands of times larger than most other body cells. To support this large volume, the muscle cells are one of the very few in the mammalian body that contain several cell nuclei. Such multinucleated cells are called syncytia. Strength-training increases muscle mass and force mainly by changing the caliber of each fiber rather than increasing the number of fibers. During such fiber enlargement muscle stem cells in the muscle tissue multiply and fuse with pre-existing fibers as to support the larger cellular volume. It has often been assumed that each nucleus can support a certain volume of cytoplasm, and hence that there is a constant volume domain served by each nucleus, although recent evidence suggests that this is an oversimplification. Until recently it was believed that during muscle wasting muscle cells lost nuclei by a nuclear self-destruct mechanism called apoptosis, but recent observations using time laps in vivoimaging in mice do not support this model. Direct observation indicated that no nuclei are lost under such conditions, and the apoptosis observed in the muscle tissue were demonstrated to occur only in other cell nuclei in the tissue, e.g. connective tissue and muscle stem cells called satellite cells. Since in vivo imaging has confirmed that cell nuclei are added during strength training and not lost upon subsequent detraining, the nuclei might provide a mechanism for muscle memory. Thus, upon retraining the extra nuclei are already there and can rapidly start synthesizing new protein to build muscle mass and strength. The extra muscle nuclei obtained by a strength training episode, seems to be very long lasting, perhaps permanent, even in muscles that are inactive for a long time. The ability to recruit new nuclei is impaired in the elderly, so it might be beneficial to strength train before senescence. Doping with anabolic steroids also seem to act partly by recruiting new nuclei. It was recently shown in mice, that a brief exposure to anabolic steroids recruited new muscle nuclei. When the steroids were withdrawn, the muscle rapidly shrank to normal size, but the extra nuclei remained. After a waiting period of 3 months, overload exercise led to a muscle growth of 36% within 6 days in the steroid-exposed group, while control muscles that had never been exposed to steroids grew only insignificantly. Since nuclei are long lasting structures in muscle, this suggests that anabolic steroids might have long lasting if not permanent effects on the ability to grow muscle mass. The mechanisms implied for the muscle memory suggest that it mainly related to strength training, and a 2016 study conducted at Karolinska Institutet in Stockholm, Sweden, failed to find a memory effect of endurance training. Recent evidence has pointed towards epigenetics as a plausible mechanism by which muscle may remember an initial bout of resistance/strength training. Indeed, via the retention of hypomethylated modifications to DNA, a recent study identified an enhanced morphological adaptation to a 7 week bout of resistance exercise, following an initial 7 week training phase and detraining phase. More work is required to build upon these, and previous findings, to identify the precise role of epigenetics in creating a memory capacity in skeletal muscle.