Glutathione (GSH) and thioredoxin (Trx), the two major biological thiol-disulfide redox systems, provide overlapping but complementary functions with respect to detoxification and maintenance of the intracellular redox state. GSH, in conjunction with GSH reductase, GSH-S-transferase, glutaredoxin, and NADPH, provides protection against a wide variety of oxidants and electrophiles. Likewise, Trx provides protection against oxidative stress through its interactions with Trx reductase, peroxiredoxins, and NADPH. GSH is present in millimolar concentrations within cells, and thus has a high capacity for detoxification. Trx, on the other hand, is present in micromolar concentrations, and, therefore, has a lower capacity than GSH for detoxification and repair. However, because Trx contains two cysteines in its active site, Trx is more suited than GSH for 2-electron reduction of proteins, as occurs in the reduction of protein disulfides. Thus, the high capacity of GSH and the efficiency of Trx complement one another in maintenance of thiol-disulfide redox environments. During recent years, considerable evidence has accumulated to show that redox signaling mechanisms function in cell regulation and growth control. Agents altering GSH concentration affect transcription of detoxification enzymes, cell proliferation and apoptosis [1]. In principle, either GSH, GSH S-conjugates, GSSG or the redox state of the GSH/GSSG couple could provide a mechanistic control or signal for functional changes. Both GSH loss and GSH oxidation have been associated with increased expression of the rate-limiting enzyme of GSH synthesis, glutamate:cysteine ligase (GLCL), and several other detoxification systems, including glutathione S-transferase (GST) and NAD(P)H: quinone reductase (N:QR). A loss or oxidation of GSH also occurs in association with differentiation both in vitro and in vivo and during apoptosis. In contrast, increases in GSH and/or a reduction of the GSH/GSSG pool are associated with growth stimulation by nutrients and growth factors. Thus, the balance of GSH and GSSG may not only reflect oxidative stress but also may reflect changes in redox signaling and control. Less is known about how the redox state of thioredoxin is maintained and the influence of Trx redox on cellular functions. In vitro assays have clearly shown that the oxidized and reduced forms of Trx