For heart, kidneys, lungs and liver alike, fibrosis represents a common pathway to their failure. Understanding pathophysiologic mechanisms involved in organ fibrosis are therefore of considerable interest, particularly given the potential for protective pharmacological strategies. Tissue repair involves inflammatory cells, including members of the monocyte/macrophage lineage, integral to initiating the repair process; and myofibroblasts, phenotypically transformed interstitial fibroblasts, responsible for collagen turnover and fibrous tissue formation. Each of these cellular events in the microenvironment of repair are associated with molecular events that lead to the de novo generation of angiotensin II (ANG II). In an autocrine/paracrine manner, this peptide regulates expression of TGF-beta 1 via angiotensin (AT1) receptor-ligand binding. It is this cytokine that contributes to phenotypic conversion of fibroblasts to myofibroblasts (myoFb) and regulates myofibroblast turnover of collagen. Angiotensin-converting enzyme (ACE) inhibition or AT1 receptor antagonism each prevent many of these molecular and cellular responses that eventuate in fibrosis and therefore have been found to be protective interventions.