PURPOSE OF REVIEW: To review the present knowledge of the role of endoplasmic reticulum (ER) stress and unfolded protein response (UPR) in the pathogenesis of fibrotic diseases. RECENT FINDINGS: ER stress and UPR occur in a number of diseases associated with organ fibrosis; however, the contribution of these pathways to the fibrotic process has not been systematically investigated. Current studies suggest that prolonged ER stress may lead to fibrosis through activation of CCAAT/enhancer-binding homologous protein-mediated apoptosis, followed by an inflammatory response and release of profibrotic cytokines. A direct profibrotic role of UPR mediators in activation of TGF-β signaling has been shown in lung fibroblasts. In addition, activation of ER stress and UPR pathways in immune cells contributes to increased production of proinflammatory cytokines. SUMMARY: Although limited in scope, current studies strongly suggest that ER stress and UPR may play an important role during development of fibrosis. Further studies are warranted to gain additional insights into the relationship between these processes.