We hypothesise that the sarcolemma of an actively growing myofibre has different properties to the sarcolemma of a mature adult myofibre. Such fundamentally different properties have clinical consequences for the onset, and potential therapeutic targets, of various skeletal muscle diseases that first manifest either during childhood (e.g. Duchenne muscular dystrophy, DMD) or after cessation of the main growth phase (e.g. dysferlinopathies). These characteristics are also relevant to the selection of both tissue culture and in vivo models employed to study such myopathies and the molecular regulation of adult myofibres. During growth, multinucleated myofibres increase enormously in size and volume with dramatic increases in length (up to ∼600 mm). This is in striking contrast with most mononucleated cells such as fibroblasts, that remain at a relatively small size (∼10–20 µm diameter). The consequences of a dynamic, expanding sarcolemma during growth, compared with that of an adult myofibre of a fixed length, are discussed with respect to various aspects of muscle biology.