Genetic and biochemical evidence has demonstrated that glutathione and glut
athione-dependent enzymes play a central role in cellular defence against t
oxic environmental agents. Modulation of cellular glutathione homeostasis c
an also have a profound effect on the sensitivity of cancer cells to a wide
range of drugs used in chemotherapy. These effects are produced by multifa
ctorial mechanisms that involve inactivation of toxic electrophiles by conj
ugation, modulation of cellular redox state, activation of drug transporter
systems and regulation of cell signalling and repair pathways. New data de
monstrating the importance of these pathways in cytoprotection and greater
understanding of the mechanisms which regulate their function reveal a numb
er of new targets for novel anti-cancer agents. It is critical, however, if
these targets are to be exploited correctly that the dynamics of glutathio
ne regulation are taken into account.