Tissues lose integrity upon injury. To rapidly restore mechanical stability, a variety of different cell types are activated to become myofibroblasts. Hallmarks of the myofibroblast are secretion of extracellular matrix, development of adhesion structures with the extracellular matrix, and formation of contractile stress fiber bundles. Rapid repair comes at the cost of tissue contracture due to the inability of the myofibroblast to regenerate tissue. When contracture and extracellular matrix remodeling become progressive and manifest as organ fibrosis, stiff scar tissue obstructs and ultimately destroys organ function. Pivotal for the formation and persistence of myofibroblasts are mechanical stimuli arising during tissue repair and chronic presence of inflammatory cells. I will provide an overview on our current projects aiming at investigating of how mechanical factors orchestrate the activation of myofibroblasts. I will focus on myofibroblast interactions with macrophages and extracellular matrix in persisting wound environments, using lung injury and implant fibrosis as paradigms. By understanding and manipulating myofibroblast mechanoperception and intercellular communication, we will be able to devise better therapies to reduce scarring and support normal wound healing in organ and implant fibrosis.