The endothelium is located in a strategic anatomical position within the blood vessel wall and thus constitutes a barrier between the blood and all tissues. The integrity of the endothelial cells, which line the entire circulatory system like wallpaper, is essential to prevent the onset of cardiovascular disorders. Aging is one of the major risk factors for the development of heart and vascular diseases. However, over the past years it has become clear that the functional capacity of endothelial cells declines with age and that physiological aging occurs independently of pathological changes. One important mechanism contributing to the onset of the aging process is the disturbance of the cellular redox homeostasis. Two key molecules involved in maintaining the delicate balance between oxidative and antioxidative systems are NADPH oxidase 4, an enzyme whose sole function is to produce reactive oxygen species and the oxidoreductase thioredoxin-1, which reduces oxidized proteins. Therefore, this review will focus on the role of these two proteins in cardiovascular aging.