| Summary: | <i>Streptomyces</i> are the most prolific source of structurally diverse microbial natural products. Advancing genome-based analysis reveals the previously unseen potential of <i>Streptomyces</i> to produce numerous novel secondary metabolites, which allows us to take natural product discovery to the next phase. However, at present there is a huge disproportion between the rate of genome reports and discovery of new compounds. From this perspective of harnessing the enduring importance of <i>Streptomyces</i>, we discuss the recent genome-directed advancements inspired by hidden biosynthetic wealth that provide hope for future antibiotics.
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