There is mounting evidence for the potential for the natural dietary antioxidant and anti-inflammatory amino acid l -Ergothioneine (ERGO) to prevent or mitigate chronic diseases of aging. This has led to the suggestion that it could be considered a ‘longevity vitamin.’ ERGO is produced in nature only by certain fungi and a few other microbes. Mushrooms are, by far, the leading dietary source of ERGO, but it is found in small amounts throughout the food chain, most likely due to soil-borne fungi passing it on to plants. Because some common agricultural practices can disrupt beneficial fungus–plant root relationships, ERGO levels in foods grown under those conditions could be compromised. Thus, research is needed to further analyse the role agricultural practices play in the availability of ERGO in the human diet and its potential to improve our long-term health.