Dystrophin is a subsarcolemmal protein which is defective in Duchenne and Becker muscular dystrophy (DMD/BMD), and in three animal models. Clinical manifestations of dystrophin deficiency in humans range from a mild calf muscle hypertrophy with cramps to the classical progressive degenerative hypertrophic myopathy of Duchenne. A common feature in the clinical presentation of dystrophin deficiency in humans and in the three documented animal models is the presence of muscle fibre hypertrophy. This paper explores the hypothesis that membrane-bound signalling processes are disrupted in the absence of dystrophin, and suggests that these abnormalities may contribute to both the hypertrophic and degenerative changes of dystrophin deficiency.