Thioredoxin 2 (Trx-2) is a small redox protein that is localized to the mitochondria and is essential for cell viability, playing a crucial role in the scavenging of ROS in mitochondria and regulating the mitochondrial apoptosis signaling pathway. Trx reductases (TrxR1 and TrxR2) are ubiquitously expressed flavoproteins that catalyze the NADPH-dependent reduction of Trx as well as several other oxidized cellular components. Mammalian Trx reductases are a part of a selenium-containing pyridine nucleotide-disulphide oxidoreductase family, which has a conserved catalytic site of Cys-Val-Asn-Val-Gly-Cys. TrxR1 and TrxR2 are also involved in the prevention of oxidative stress. Inhibition of TrxR activity may provide for potential treatments of cancer, AIDS and other autoimmune diseases as well as bacterial infections and parasitic diseases.