Muscular dystrophies are a group of diseases that primarily affect skeletal muscle and are characterized by progressive muscle wasting and weakness. Although these diseases have been clinically recognized for a number of years, genetic defects in a number of muscular dystrophies have only recently been identified. One of the most important advances in understanding the molecular genetics of neuromuscular diseases has been the cloning of the gene encoding dystrophin, the protein absent in muscle of Duchenne muscular dystrophy (DMD) patients. In the last few years, the role of dystrophin in skeletal muscle has been studied, and several dystrophin-associated proteins (DAPs) have been identified. Components of the dystrophin-glycoprotein complex are now being characterized, and evidence is beginning to indicate that proteins of this complex may be responsible for other forms of muscular dystrophy. The present review focuses on the molecular basis of three muscular dystrophies (DMD, severe childhood autosomal recessive muscular dystrophy [SCARMD], and congenital muscular dystrophy [CMD]) that may be caused by disruptions in the dystrophin-glycoprotein complex, which normally links the subsarcolemmal cytoskeleton to the extracellular matrix in skeletal muscle.