Mushrooms are abundant sources of a wide range of useful natural products. Nowadays, commercial mushroom products are from mushrooms collected from field cultivation, which is a time-consuming and labor-intensive process. Submerged cultivation of mushrooms has significant industrial potential, but its success on a commercial scale depends on cost compared with existing technology. Increasing product yields and development of novel production systems that address the problems associated with this new technology will certainly facilitate expansion. This article outlines the major valuable metabolites produced by mushroom cultivation and advances in submerged culture of mushrooms, taking Ganoderma lucidum, a popular folk and an oriental medicine used to treat many diseases, as a typical example. Our latest data on mushroom cultivation for efficient production of bioactive ganoderic acids and Ganoderma polysaccharides in bioreactors are presented.