We propose that the diet-derived compound ergothioneine (ET) is an important nutrient in the human body, especially for maintenance of normal brain function, and that low body ET levels predispose humans to significantly increased risks of neurodegenerative (cognitive impairment, dementia, Parkinson's disease) and possibly other age-related diseases (including frailty, cardiovascular disease, and eye disease). Hence, restoring ET levels in the body could assist in mitigating these risks, which are rapidly increasing due to ageing populations globally. Prevention of neurodegeneration is especially important, since by the time dementia is usually diagnosed damage to the brain is extensive and likely irreversible. ET and vitamin E from the diet may act in parallel or even synergistically to protect different parts of the brain; both may be “neuroprotective vitamins”. The present article reviews the substantial scientific basis supporting these proposals about the role of ET.