It is increasingly recognized that tissue-specific nutrient deficiencies can exist in the absence of whole-body deficiency and that these deficiencies may result from disease or disease-related physiological processes. Brain and central nervous system tissues require adequate nutrient levels to function. Many nutrients are concentrated in the cerebrospinal fluid relative to the serum in healthy individuals, and other nutrients resist depletion in the presence of whole-body nutrient depletion. The endothelial, epithelial, and arachnoid brain barriers work in concert to selectively transport, concentrate, and maintain levels of the specific nutrients required by the brain while also blocking the passage of blood-borne toxins and pathogens to brain and central nervous system tissues. These barriers preserve nutrient levels within the brain and actively concentrate nutrients within the cerebrospinal fluid and brain. The roles of physical and energetic barriers, including the blood–brain and blood–nerve barriers, in maintaining brain nutrient levels in health and disease are discussed.