Rapid repair and restoration of tissue integrity after injury is vital for organismal survival. Some lower vertebrates and invertebrates possess the extraordinary ability to regenerate functional tissues throughout their lifetime (1). In mammals, however, tissue regeneration is largely restricted to gestation. In the terrestrial environment, evolutionary pressures to heal have favored the rapid formation of fibrotic tissue (or scar tissue) instead of recreating original tissue architecture (2). Scarring-related tissue dysfunction remains a major health care challenge with limited treatment options. Thus, scar prevention and regeneration of functional tissues is a coveted goal of tissue repair. On page 362 of this issue, Mascharak et al. (3) point to a therapeutic target for tissue regeneration by revealing how specific fibroblasts produce scars in response to skin wounding.