Ecologically, edible mushrooms can be: (i) parasites of plants or animals, (ii) saprotrophs, which live and feed on dead organisms, such as the industrially cultivated button, oyster or shiitake mushrooms, or (iii) ectomycorrhizal, which establish mutually beneficial symbiosis with the roots of host plants. Ectomycorrhizal wild mushrooms, which are the subject of this chapter, embrace the most expensive edible fungi, including truffles, porcini, matsutake, chanterelles, Caesar's mushrooms, or saffron milk caps. The international commerce of edible ectomycorrhizal mushrooms (EEMs) annually is worth billions of dollars. However, EEMs have been a largely unexplored source of bioactive compounds. Despite this fact, analgesic, antiallergic, anticarcinogenic, antibacterial, anticoagulant, antifungal, antihypertensive, anti-inflammatory, antinociceptive, antioxidant, antipyretic, antivenom, antiviral (including anti-HIV), cholesterol-lowering, hepatoprotective, and immune enhancement properties have been found in more than 100 species of EEMs. Some bioactive compounds including grifolin, polyozelyn, and novel lectins or ribonucleases produced by Albatrellus, Boletopsis, Hygrophorus, Thelephora, and Polyozellus, respectively, are exclusive of EEMs. Additionally, insecticide, nematicide, and allelophatic compounds with potential application to control agricultural pests and weeds have been found in EEM. Despite the fact that most EEMs have defied cultivation, some advances have been made in cultivation of truffles and broth cultures of species included in the genera Hygrophorus, Lactarius, Morchella, Rhizopogon, Suillus, and Tuber as a potential source of bioactive compounds with medical or nutraceutical importance. In addition, EEMs as a valuable non-timber forest product contributes to rural development and the establishment of truffle plantations contributes to rehabilitation of degraded areas and global carbon sequestration. In the future, advances in the cultivation of EEMs might produce bioactive compounds in industrial amounts. © Springer International Publishing Switzerland 2014. All rights are reserved.