Duchenne muscular dystrophy (DMD) is the most common of the human muscular dystrophies, affecting approximately 1 in 3500 boys. Most DMD patients die in their late teens or early twenties due to involvement of the diaphragm and other respiratory muscles by the disease. The primary abnormality in DMD is an absence of dystrophin, a 427 kd protein normally found at the cytoplasmic face of the muscle cell surface membrane. Based upon the predicted structure and location of the protein, it has been proposed that dystrophin plays an important role in providing mechanical reinforcement to the sarcolemmal membrane of muscle fibers. Therefore, dystrophin could help to protect muscle fibers from potentially damaging tissue stresses developed during muscle contraction. In the present paper, the nature of mechanical stresses placed upon myofibers during various forms of muscle contraction are reviewed, along with current lines of evidence supporting a critical role for dystrophin as a subsarcolemmal membrane-stabilizing protein in this setting. In addition, the implications of these findings for exercise programs and other potential forms of therapy in DMD are discussed.