Throughout evolution, humans have experienced a series of natural selections, which have included a physiological resistance during seasonal food shortages or unpredictable feast–famine cycles. Therefore, the capacity for surviving starvation has been proposed to play a role in human evolution. There are benefits to health that are associated with a lifestyle of sustained mild starvation. For example, dietary caloric restriction (CR) has been shown to slow aging, increase life span, and maintain health, function, and vitality. Benefits to metabolism and health have also been shown for specific amino acid restriction, for example, restriction of the sulfur amino acid methionine. To provide an opportunity for leaders in the field of aging and dietary restriction to share current research and plan future investigations, the Orentreich Foundation for the Advancement of Science (OFAS) sponsored the symposium Diet, Sulfur Amino Acids, and Healthspan, on September 21 and 22, 2015, in Tarrytown, New York. This Annals volume presents a collection of papers stemming from this symposium, exploring the effects of dietary and sulfur amino acid restriction on health span, aging, and disease progression, from the molecular to the phylogenic level.