Although there has been a steady decline in natural product discovery efforts in the pharmaceutical industry over the last three decades, natural product chemical scaffolds have continued to yield important human antimicrobial agents, immunomodulators, and antitumor agents, as well as plant crop protectants. Natural product discovery is currently undergoing a renaissance based to a large extent on the observations from microbial genome sequencing projects indicating that only a fraction of the potential microbial secondary metabolites from actinomycetes, other eubacteria, and fungi have been discovered so far, and that most secondary metabolite pathways are not expressed under normal laboratory growth conditions. However, the new discipline of “genome mining” has been exploring ways to activate the expression of these “cryptic pathways.”