Mushrooms are part of fungal biota characterized by wonder. They rise up from lignocellulosic wastes: yet they become so bountiful and nourishing. Mushrooms are environmentally friendly. They biosynthesize their own food from agricultural crop residues, which would otherwise cause health hazards. The extant records show the continued use of some mushrooms, e.g., Lentinus edodes, Ganoderma lucidum, and Cordyceps sinensis are now centuries old. This review presents a pyramid model for mushroom uses (industries), as food, dietary supplements (tonic), and medicine. A regular intake of mushrooms can make us healthier, fitter, and happier, and help us live longer. The sense of purpose and vision for the mushroom industries is also briefly discussed. A variety of mushrooms have been used traditionally in many different cultures for the maintenance of health and in the prevention and treatment of various diseases. A total of 126 medicinal functions are thought to be produced by medicinal mushrooms (MM) and fungi, including antitumor, immunomodulating, antioxidant, radical scavenging, cardiovascular, anti-hypercholesterolemia, antiviral, antibacterial, anti-parasitic, antifungal, detoxification, hepatoprotective, and anti-diabetic effects. Special attention is paid to mushroom polysaccharides. Many, if not all, higher Basidiomycetes mushrooms contain biologically active polysaccharides in fruit bodies, cultured mycelium, and cultured broth. The data on mushroom polysaccharides are summarized for approximately 700 species of higher Hetero- and Homobasidiomycetes. In particular, the most important for modern medicine are polysaccharides with antitumor and immunostimulating properties. Several of the mushroom polysaccharide compounds have proceeded through phase I, II, and III clinical trials and are used extensively and successfully as drugs in Asia to treat various cancers and other diseases. Mushrooms are superior sources of different types of dietary supplements (DSs) (tonics). The advantages of using mushroom-based DSs as a matter of safety (as opposed to herbal preparations) are: (1) The overwhelming majority of mushrooms used for production of DSs are cultivated commercially (and not gathered in the wild). (2) Mushrooms are easily propagated vegetatively and thus keep to one clone. The mycelium can be stored for a long time, and the genetic and biochemical consistency can be checked after a considerable time. (3) The main advantage, in our opinion, is that many mushrooms are capable of growing in the form of mycelial biomass in submerged cultures. In this review, we discuss legal and regulatory issues introducing and controlling DSs from MMs in different countries, including the United States, the European Community, Australia, New Zealand, Japan, and P.R. China, and guidelines of the World Health Organization. One of the targets of the present review is also to draw attention to many critically important unsolved problems in the future development of medicinal mushroom science in the 21st century.