Heat shock proteins (HSPs) are key regulators of cell homeostasis, and their cytoprotective role has been largely investigated in the last few decades. However, an increasing amount of evidence highlights their deleterious effects on several human pathologies, including cancer, in which they promote tumor cell survival, proliferation and drug resistance. Therefore, HSPs have recently been suggested as therapeutic targets for improving human disease outcomes. Fibrotic diseases and cancer share several properties; both pathologies are characterized by genetic alterations, uncontrolled cell proliferation, altered cell interactions and communication and tissue invasion. The discovery of new HSP inhibitors that have been shown to be efficacious against certain types of cancers has given rise to a new field of research that investigates the activity of these compounds in other incurable human diseases such as fibrotic disorders. The aim of this review is to discuss new findings regarding the involvement of HSPs in the pathogenesis of organ fibrosis and to note recent discoveries that indicate that HSPs could be important therapeutic targets to improve the current dismal outcome of fibrotic diseases.