Thioredoxin-1 (Trx-1) is a multifunctional protein ubiquitously found in the human body. Trx-1 plays an important role in various cellular functions such as maintenance of redox homeostasis, proliferation, and DNA synthesis, but also modulation of transcription factors and control of cell death. Thus, Trx-1 is one of the most important proteins for proper cell and organ function. Therefore, modulation of Trx gene expression or modulation of Trx activity by various mechanisms, including post-translational modifications or protein–protein interactions, could cause a transition from the physiological state of cells and organs to various pathologies such as cancer, and neurodegenerative and cardiovascular diseases. In this review, we not only discuss the current knowledge of Trx in health and disease, but also highlight its potential function as a biomarker.