Glutathione (GSH) is the major non-protein thiol in cells and is a co-factor for many types of conjugation reactions involving glutathione S-transferases (GST). Because of the defined role of GST in drug metabolism, elevated expression of GSTpi either as a tumor marker or in drug resistance has automatically been linked to detoxification. Similarly, GSH has mostly been viewed as a passive cellular supply of nucleophilic sulfur. This mini-review highlights recent reports which advocate a novel, non-catalytic role for GSTpi as an integral determinant of cellular pathways of stress response, proliferation and apoptosis. Copyright 1999 Harcourt Publishers Ltd.