Since the discovery of vitamins over 100 years ago, there have been debates and controversies regarding their true efficacy on health. With regards to preventing age-related degenerative conditions, we encounter a considerable degree of exaggerated claims, and at the same time, hidden benefits, which are unveiled by continuing research. In this chapter there is a balanced discussion based on a synthesis of the latest findings regarding all existing vitamins, with an emphasis on improving overall health outcomes. Apart from the well-accepted actions of vitamins, other emerging and less well-known benefits of supplementation will be examined, with emphasis on the latest research. Dosage, specific active configurations of each vitamin (vitamers), the presence or not of deficiency, the aim of the treatment, combinations of vitamins and of other active nutrients, all are parameters which define the final effectiveness of vitamins. It will be shown that most vitamins do have a positive effect for maintaining health and preventing age-related degenerative conditions, particularly in cases of deficiency, when used in combination, in a focused manner, and in accordance with hormetic principles.