Calorie restriction has been known for many decades to extend the life span of rodents. Since the more recent discovery that a long-term reduction in nutrient intake also extends life span in nearly every invertebrate model organism used for aging research, the mechanisms behind the longevity benefits of this intervention have been under intense scrutiny. While models have been developed in yeast, worms, and flies, the molecular mechanisms governing life span extension by calorie restriction remain controversial, resulting in great anticipation of mammalian studies testing these models. Here we discuss the links between nutrient reduction and enhanced longevity with emphasis on evolutionarily conserved nutrient response signaling.