A variety of diseases that are characterized by fibrosis share common features including the proliferation of fibroblasts and the deposition of extracellular matrix. Fibrosis often begins as an inflammatory reaction with leukocyte infiltration followed by the elaboration of cytokines. Here, Elizabeth J. Kovacs argues that the aberrant production of these mediators sustains the connective tissue accumulation that results in permanent alteration in tissue structure and function.