Although the button mushroom (Agaricus bisporus) accounts for slightly over half of total world mushroom production, specialty mushrooms, e.g., shiitake (Lentinula edodes), straw (Volvariella volvacea), oyster (Pleurotus spp.), and enokitake (Flammulina velutipes), are increasing in popularity. These species contain moderate quantities of good quality protein and are good sources of dietary fiber, vitamin C, B vitamins, and minerals. Lipid levels are low, but unsaturated to saturated fatty acid ratios are high (about 2.0 – 4.5:1). Some species (e.g., shiitake) accumulate cadmium and selenium and other heavy metals, and some may contain toxic substances such as the heat labile cardiotoxic proteins volvatoxin in the straw mushroom and flammutoxin in enokitake. Extensive clinical studies, primarily in Japan, have clearly demonstrated that a number of species have medicinal and therapeutic value, by injection or oral administration, in the prevention/treatment of cancer, viral diseases (influenza, polio), hypercholesterolemia, blood platelet aggregation, and hypertension. Most of the studies have focused on shiitake, enokitake, Pleurotus spp., and on the generally nonculinary Ganoderma spp. Many of the active substances which include polysaccharides (e.g., β-glucans), nucleic acid derivatives (the hypocholesterolemic eritadenine), lipids, peptides, proteins, and glycoproteins, have been isolated and identified. Some of the mechanisms of activity have been elucidated, e.g., antiviral activity via stimulation of interferon production in the host. Additional medical claims less well documented may nonetheless have some validity and merit further study.