Thioredoxins (Trxs) are low-molecular-weight proteins that participate in the reduction of target enzymes. Trxs contain a redox-active disulfide bond, in the form of a WCGPC amino acid sequence motif, that enables them to perform dithiol-disulfide exchange reactions with oxidized protein substrates. Widely distributed across the three domains of life, Trxs form an evolutionarily conserved family of ancient origin. Thioredoxin reductases (TRs) are enzymes that reduce Trxs. According to their evolutionary history, TRs have diverged, thereby leading to the emergence of variants of the enzyme that in combination with different types of Trxs meet the needs of the cell. In addition to participating in the regulation of metabolism and defense against oxidative stress, Trxs respond to environmental signals-an ability that developed early in evolution. Redox regulation of proteins targeted by Trx is accomplished with a pair of redox-active cysteines located in strategic positions on the polypeptide chain to enable reversible oxidative changes that result in structural and functional modifications target proteins. In this review, we present a general overview of the thioredoxin system and describe recent structural studies on the diversity of its components.