Skeletal muscle cytoskeletal proteins are receiving more attention recently based on their importance in maintaining muscle integrity, their role in transmitting force throughout the cell, and their involvement in muscle diseases. In this report, the authors focus on the intermediate filament system of skeletal muscle composed of the protein desmin. Desmin is shown to transmit force from myofibrillar force generators to the muscle surface and to the muscle-tendon junction. This protein is lost rapidly during high-intensity exercise using a rabbit model. Mice were genetically engineered that lack the desmin gene and these muscles were shown to generate lower stress but actually to experience less injury during intense exercise. Finally, direct imaging of muscle cells with fluorescently labeled cytoskeletal proteins shows that lack of the desmin protein results in tremendous disorganization of the myofibrillar lattice which may help to explain desmin myopathies.