The present invention is directed to compositions and methods for the prevention, inhibition, and/or treatment of progressive fibrosis present in various fibroproliferative disorders. In particular, embodiments of the present invention relate to the use of Sigma-1 receptor agonists for use in the treatment or prevention of progressive fibrosis characterized by the overproliferation of ECM producing cells, e.g. myofibroblasts and by the excessive deposition of ECM components in a medical or disease condition. Preferred Sigma-1-receptor agonists are disclosed.