The thioredoxin-1 (Trx-1) system consists of two oxidoreductases, thioredoxin reductase and Trx-1. Trx-1 is a ubiquitously expressed oxidoreductase. The cellular functions of Trx-1 are wide range. They include protein disulfide reduction, DNA synthesis, protection from apoptosis, redox regulation of a variety of proteins, transcription factors and reduction of H(2)O(2), respectively. This review will first focus on the essential role for Trx-1 in different cardiovascular cells, namely smooth muscle cells, endothelial cells, and cardiomyocytes. Thereby, the review will demonstrate the predominant role of Trx-1 to limit oxidative stress directly due to reactive oxygen species scavenging and by protein-protein interaction with key signaling molecules. Second, this review will highlight the role of Trx-1 in cardiovascular aging, focusing on its importance on shear stress and the profound changes with age. Finally, the review will focus on important in vivo studies showing a protective role of Trx-1 in different cardiovascular diseases. Thus, the Trx system and Trx-1 could be important future targets to develop clinical therapies for cardiovascular disorders.