Mushrooms have been used both as food and as medicine in many cultures, and their popularity as both is growing in the United States. We have shown that they are inherently, or can easily be made to be, excellent dietary sources of 4 important bioactive compounds that are all known to decease in humans as they age. These are the micronutrients selenium and vitamin D2 and antioxidants glutathione and ergothioneine (Ergo). All of these except for Ergo can be found in significant amounts in other foods; hence, it will be the primary focus of this review. Because Ergo is made in nature primarily by nonyeast fungi, mushrooms are by far the best human dietary source. Humans produce a highly specific transport protein for Ergo that makes it highly bioavailable and avidly retained, leading many to speculate about its potential importance to human health because such specific transporters are rarely present for nonnutrient bioactive compounds. Ergo is found in small amounts throughout the food chain presumably owing to fungi in the soil passing it on to plants and then animals that eat them. We have preliminary evidence that Ergo levels in the American food supply might be compromised because of reduced fungal populations in agricultural soils caused by some cultivation practices. Relationships observed between estimated Ergo consumption and average longevity and reductions in chronic neurodegenerative diseases across different countries supports additional interest in Ergo as a dietary chemopreventive agent for aging-related diseases.