Regular consumption of cruciferous vegetables or spices is associated with a reduced incidence of cancer and reduction of markers for neurodegenerative damage. Furthermore, greater health benefit may be obtained from raw as opposed to cooked vegetables. Nutritional interventions, by increasing dietary intake of fruits and vegetables, can retard and even reverse age-related declines in brain function and cognitive performance. The mechanisms through which such dietary supplementation may diminish free radical-related diseases is related to their ability to reduce the formation of reactive oxygen and nitrogen species, along with the up-regulation of vitagenes, such as members of the heat shock protein (Hsp) family, heme oxygenase-1 and Hsp70. The most prominent dietary factor that increases the risk of many different chronic diseases is excessive calorie intake. Reducing energy consumption by controlled caloric restriction or intermittent fasting increases lifespan and protects various tissues against diseases, in part, by hormetic mechanisms that increase cellular stress resistance. This biphasic dose-response relationship (i.e., hormesis) displays low-dose stimulation and a high-dose inhibition. Despite the current interest in hormesis by the toxicology community, quantitatively similar U-shaped dose responses have long been recognized by researchers to be involved with factors affecting memory, learning, and the occurrence of oxidative stressmediated degenerative responses. Dietary polyphenols also act hormetically, displaying cytoprotective effects at low doses. However, excessive nutritional supplementation (i.e., high doses) can have negative consequences through the generation of more reactive and harmful intermediates with pathological consequences.