The myofibroblast has been shown to have a key role in tissue reconstruction after injury and pathological changes characterized by fibrosis. Force generation by the myofibroblast depends on the isometric contraction of stress fibers containing alpha-smooth muscle actin, and is mediated through Rho/Rho-kinase. The force is transmitted by vinculin and tensin-containing "supermature" focal adhesions, which connect stress fibers with the extracellular matrix. Force production and transmission by the myofibroblast are modulated by the coordinated action of cytokines, extracellular matrix components and mechanical tension. Regulation of these phenomena will be important for therapeutic strategies aimed at influencing fibrocontractive diseases.