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Natural metabolites from microorganisms play significant roles in the discovery of drugs, both for disease treatments in humans, and applications in agriculture. The Basidiomycetes <i>Stereum</i> genus has been a source of such bioactive compounds. Here we report on the structures and activities of secondary metabolites from <i>Stereum</i>. Their structural types include sesquiterpenoids, polyketides, vibralactones, triterpenoids, sterols, carboxylic acids and saccharides. Most of them showed biological activities including cytotoxic, antibacterial, antifungal, antiviral, radical scavenging activity, autophagy inducing activity, inhibiting pancreatic lipase against malarial parasite, nematocidal and so on. The syntheses of some metabolites have been studied. In this review, 238 secondary metabolites from 10 known species and various unidentified species of <i>Stereum</i> were summarized over the last seven decades.