Striving for longevity is neither a recent human desire nor a novel scientific field. The first article on this topic was published in 1838, when the average human life expectancy was approximately 40 years. Although nowadays people on average live almost as twice as long, we still (and perhaps more than ever) look for new ways to extend our lifespan. During this seemingly endless journey of discovering efficient methods to prolong life, humans were enthusiastic regarding several approaches, one of which is caloric restriction (CR). Where does CR, initially considered universally beneficial for extending both lifespan and health span, stand today? Does a lifelong decrease in food consumption represent one of the secrets of centenarians' long and healthy life? Do we still believe that if we eat less, we will live longer? This review aims to summarize the current literature on CR as a potential life-prolonging intervention in humans and discusses metabolic pathways that underlie this effect.