Glutathione and glutathione-dependent enzymes are ubiquitously distributed through nature. These enzyme systems appear to have evolved to protect cells from toxic and mutagenic environmental chemicals. There is now unequivocal evidence demonstrating that these enzymes play a role in chemical resistance in a variety of phylogeny including, bacteria, plants and insects. There is also increasing circumstantial, as well as genetic evidence which indicates that these enzymes are also a determinant in the sensitivity of tumor cells to anticancer drugs, particularly alkylating agents and those drugs whose toxic effects are mediated by free radicals. In this review some of the experimental data which leads to these conclusions is discussed.