Fibrosis, so-called scarring, is a key cause of pathology and dysfunction in a variety of organs. The biology of healing and scarring are similar, albeit with very different outcomes. Typical of this process in general, renal fibrosis is the result of a disproportionate accumulation of extracellular matrix that occurs in ongoing kidney disease. Renal scarring is both progressive and multifactorial, ultimately leading to end-stage renal failure and the requirement for dialysis or kidney transplantation. Regardless of the underlying etiology, renal mesenchymal cells such as fibroblasts are the cellular basis of this process. Activity and differentiation of these cells are regulated by a number of profibrotic cytokines, growth factors, vasoactive mediators, and other signals, with transforming growth factor-beta being among the most important. However, we now also recognize that there are a number of endogenous antifibrotic factors that are renoprotective by counteracting these signals to limit matrix synthesis and organization and reduce net accumulation. Relaxin is one such factor. The absence of endogenous relaxin results in spontaneous fibrosis with aging and also accelerates the pathogenesis of progressive fibrosis after injury. Both effects are reversed by replenishment with recombinant H2 relaxin. This review summarizes recent developments in the understanding of the cellular and molecular mechanisms in fibrosis and how these are influenced by relaxin.