Thioredoxin (Trx), a small, ubiquitous thiol [sulfydryl (-SH)] protein, is one of the most important regulators of reduction–oxidation (redox) balance and, thus, redox-controlled cell functions. Although Trx was discovered 40 years ago in bacteria, the number and diversity of processes that Trx influences in human cells have only been appreciated recently. Processes influenced by Trx include the control of cellular redox balance, the promotion of cell growth, the inhibition of apoptosis and the modulation of inflammation. Not surprisingly, the role of Trx in a wide range of human diseases and conditions, including cancer, viral disease, ischaemia–reperfusion injury, cardiac conditions, aging, premature birth and newborn physiology, is subject to intense investigation. However, whether Trx contributes to or prevents the pathology of a particular condition is not always clear. In this article, we review the role of Trx in human disease and relate this to its redox activity and biological properties, and discuss the development and use of therapies that either inhibit or augment Trx activity.