Thioredoxins (Trxs) are a group of small ubiquitous proteins in all living cells that are key regulators of cellular redox balance. The mammalian Trx family has three members: Trx-1, Trx-2, and TrxL. Trx-1 is the only extracellular occurring thioredoxin, and is secreted by lymphocytes, hepatocytes, fibroblasts, and several tumor cells. Plasma concentrations of Trx-1 are up to 6 nM. In cells, Trx-1 is localized predominantly in the cytoplasm. Small amounts have been detected in the nucleus and in association with the outside surface of the cells. Expression of Trx-1 is increased under various stress conditions such as hypoxia, elevated hydrogen peroxide concentrations, photochemical oxidative stress, and viral and bacterial infections. Biological functions of Trx-1 include growth factor activity, antioxidant properties, a cofactor that provides reducing equivalents, and transcriptional regulation. The synovial tissue of rheumatoid arthritis patients produces increased levels of Trx-1 under oxidative stress conditions, and a correlation exists between the plasma levels of Trx-1 and the severity of the disease, making Trx-1 a biomarker for this pathological condition.