GST isozymes are an important part of the normal cellular defense against toxic xenobiotics and carcinogens. These multifunctional proteins can interact with a broad range of substrates in a variety of ways. In particular, GSTs have been implicated in the detoxication of many antineoplastic agents. Elevated levels of certain GST isozymes have been associated with malignant transformation and with experimental drug resistance. Although the role of GST in antineoplastic drug resistance is unclear, recent studies have shown increased activity of GST in many human tumors relative to normal tissues. These findings raise the possibility that the presence of certain GST isozymes may be a marker for malignant transformation in some human tumors, and that GSTs may play a role in de novo and acquired drug resistance. Identifying the factors which regulate the expression of these drug-metabolizing enzymes as well as agents which inhibit their activities may provide new insights into the therapy of tumors clinically refractory to chemotherapy.