Caloric restriction (CR) without malnutrition in mice and rats reduces the incidence of spontaneous tumors and delays their appearance while increasing maximum life span. These results depend largely on CR per se, and not on low intakes of fat or other nutrients. Although most studies have tested CR imposed early in life, CR started in midadulthood also retards cancer and aging. The way(s) by which CR impedes cancers remain unclear, but possibilities include less cellular oxidative damage, retarded immunologic aging, hormonal changes, less energy available for cell proliferation, reduced exposure to dietary carcinogens and promoters, enhanced DNA repair, and less carcinogen activation. Far less is known about the relationship between caloric intake and cancer incidence in humans; however, recent findings suggest a positive association for certain cancers.