Mushrooms are macroscopic fungi which can be either epigeous or hypogeous and is estimated to be 140,000 on earth, yet only 10% are known. Since ancient time, it played a diverse role in human history for mycolatry, mycophagy and as medicine in folklore and religion. Many Asian and western countries consider mushrooms as panacea for a large number of diseases and utilized for consumption as a gourmet food for its taste as well as flavor. In recent years, scientific research fraternities have confirmed that various extracts and metabolites of mushrooms used traditionally are able to treat a wide range of diseases due to their balanced modulation of multiple targets thereby providing a greater therapeutic effect or equivalent curative effect to that of modern medicine. Medicinal mushrooms especially those belonging to higher basidiomycete groups are reservoir of bioactive compounds with multiple therapeutic properties. The present review provides historical importance as well as an updated information on pharmacologically relevant higher basidiomycetes belong to the genus Agaricus, Auricularia, Phellinus, Ganoderma, Pleurotus, Trametes and Lentinus and their biologically active secondary metabolites. This will help the researchers to understand various type of secondary metabolites, their therapeutic role and related in vivo or in vitro work at a glance. The mounting evidences from several scientific community across the globe, regarding various therapeutic applications of mushroom extracts, unarguably make it an advance research area worth mass attention.