The lungs are the richest in oxygen among the various organs of the body and are always subject to harmful reactive oxygen species. Regulation of the reduction/oxidation (redox) state is critical for cell viability, activation, proliferation, and organ functions. Although the protective importance of various antioxidants has been reported, few antioxidants have established their clinical usefulness. Thioredoxin (TRX), a key redox molecule, plays crucial roles as an antioxidant and a catalyst in protein disulfide/dithiol exchange. TRX also modulates intracellular signal transduction and exerts antiinflammatory effects in tissues. In addition to its beneficial effects in other organs, the protective effect of TRX in the lungs has been shown against ischemia/ reperfusion injury, influenza infection, bleomycin-induced injury, or lethal inflammation caused by interleukin- 2 and interleukin-18. Monitoring of TRX in the plasma, airway, or lung tissue may be useful for the diagnosis and follow-up of pulmonary inflammation. Promotion/modulation of the TRX system by the administration of recombinant TRX protein, induction of endogenous TRX, or gene therapies can be a therapeutic modality for oxidative stress-associated lung disorders.