The dystrophin-glycoprotein complex (DGC) is a multimember complex that connects the cytoskeleton of a muscle fiber to its surrounding laminin containing extracellular matrix. The main components of the DGC are dystrophin, dystroglycan and the sarcoglycan complex. Mutations in any of these components lead to various forms of muscular dystrophy and often cardiomyopathy. The DGC is not only expressed in skeletal and heart muscle cells but also in vascular smooth muscle cells as well as in endothelial cells. The DGC has been extensively studied in skeletal muscle, but its role in vasculature is less clear. I will discuss a few studies in which the roles of DGC components in vascular smooth muscle have been examined and how absence of vascular DGC impacts muscular dystrophy. For example, it has been demonstrated that sarcoglycan deficient animals display vascular dysfunction that contributes to development of muscular dystrophy and cardiomyopathy. However, it remains controversial how these vascular spasms arise. Moreover, dystrophin deficient smooth muscle contributes to the dystrophic phenotypes of Duchenne muscular dystrophy (the most common type of muscular dystrophy). Finally, we have recently in collaboration with Anna Hultgårdh-Nilsson begun to analyze the roles of laminins and DGC components in the atherosclerotic process. We have demonstrated that dystrophin deficiency in mice stimulates neointima formation. Hence, dystrophin in vascular smooth muscle cells may protect the vessel wall against injury and atherosclerosis. Consequently, boys with Duchenne muscular dystrophy may be more susceptible to the development of atherosclerotic lesions and may more easily develop restenotic lesions in response to angioplasty.